The DOI matches its Crossref record; 61 of the 65 references it cites were found in a registry or an index; 38 of the 54 sources its claims cite were checked for support.
Gain-of-function mutation of microRNA-140 in human skeletal dysplasia
Open accessAbstract
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Heterozygous loss-of-function point mutations of miRNA genes are associated with several human congenital disorders1–5, but neomorphic (gain-of-new-function) mutations in miRNAs due to nucleotide substitutions have not been reported. Here we describe a neomorphic seed region mutation in the chondrocyte-specific, super-enhancer-associated MIR140 gene encoding microRNA-140 (miR-140) in a novel autosomal dominant human skeletal dysplasia. Mice with the corresponding single nucleotide substitution show skeletal abnormalities similar to those of the patients but distinct from those of miR-140-null mice6. This mutant miRNA gene yields abundant mutant miR-140-5p expression without miRNA-processing defects. In chondrocytes, the mutation causes widespread derepression of wild-type miR-140-5p targets and repression of mutant miR-140-5p targets, indicating that the mutation produces both loss-of-function and gain-of-function effects. Furthermore, the mutant miR-140-5p seed competes with the conserved RNA-binding protein Ybx1 for overlapping binding sites. This finding may explain the potent target repression and robust in vivo effect by this mutant miRNA even in the absence of evolutionary selection of miRNA–target RNA interactions, which contributes to the strong regulatory effects of conserved miRNAs7,8. Our study presents the first case of a pathogenic gain-of-function miRNA mutation and provides molecular insight into neomorphic actions of emerging and/or mutant miRNAs. Clinical insights from patients with a rare genetic skeletal disorder led to the discovery of the first case of a pathogenic gain-of-function miRNA mutation.
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TL;DR
The paper reports a heterozygous neomorphic seed-region mutation in MIR140 (miR-140-5p) causing a novel autosomal dominant skeletal dysplasia, with mutant miRNA producing both loss- and gain-of-function effects. Mouse knock-in models recapitulate key skeletal abnormalities distinct from miR-140-null mice, and mutant miR-140-5p competes with Ybx1 at overlapping RNA binding sites.
Key findings
- The same heterozygous substitution, chr16:g.69967007A>G (MIR140:NR_029681.1:n.24A>G), was found in three affected individuals from two unrelated families; it occurred de novo in P1 and P3, co-segregated in Family 1, and was absent from gnomAD. Clinical features included disproportionate short stature, short limbs, small hands and feet, midface hypoplasia, mild spondylar dysplasia, delayed epiphyseal ossification, and severe brachydactyly with cone-shaped phalangeal epiphyses.
- CRISPR-Cas9 knock-in mice with the corresponding Mir140 A>G substitution showed delayed secondary ossification, decreased Col10a1 expression, delayed cartilage maturation of larynx/trachea/anterior ribs, severely decreased epiphyseal mineralization, mildly flat vertebral bodies, and a wider basal skull growth plate; these features were distinct from miR-140−/− mice.
- Small RNA sequencing showed the mutation yielded slightly greater mutant miR-140-5p than wild-type miR-140-5p and decreased two miR-140-3p species, without miRNA-processing defects. RNA-seq showed widespread derepression of wild-type miR-140-5p targets and repression of mutant miR-140-5p targets, including Loxl3, Btg1, and Trps1; the hypoxia pathway was impaired in miR-140G/G but not miR-140−/− chondrocytes, with reduced Hif1a and collagen crosslinking.
- Ago2 and Ybx1 seCLIP analyses indicated that the mutant miR-140-5p seed competes with Ybx1 for overlapping binding sites, especially in 3′ UTRs; Ybx1 inhibition dampened mutant miRNA-mediated repression. The authors describe this as the first case of a pathogenic gain-of-function miRNA mutation.
Methods
- Clinical and genetic study of two unrelated families: exome sequencing, whole genome sequencing, Sanger sequencing, and comparative genomic hybridization; the MIR140 variant was identified and confirmed in affected individuals.
- Mouse model: CRISPR-Cas9 knock-in of the Mir140 A>G substitution; heterozygous (miR-140G/+), homozygous (miR-140G/G), wild-type (miR-140+/+), and miR-140−/− mice were compared using skeletal preparations, histology, micro-CT, BrdU labeling, TUNEL staining, and collagen crosslink analysis.
- Molecular analyses in primary rib chondrocytes and cell lines: small RNA sequencing, RNA sequencing, qRT-PCR, Western blot, luciferase reporter assays, single-cell dual fluorescence reporter assays, Ago2 and Ybx1 seCLIP, TargetScan prediction, GSEA, and RBP motif analysis.
Limitations
- Stated: seCLIP had low sensitivity for small starting materials such as primary chondrocytes, and intronic seCLIP clusters were considered non-specific; sample sizes were estimated based on prior experience, with examined mouse numbers in Supplementary Table 2; human genome data are protected by Swedish law, with raw Sanger sequencing data available upon request.
- Evident: the human genetic evidence comes from only three affected individuals in two families, limiting broader genotype–phenotype generalization.
- Evident: much of the mechanistic evidence relies on mouse chondrocytes and heterologous cell assays, and the paper does not report an independent human cohort validating the proposed Ybx1 competition mechanism.
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84 Own result · 28 Own interpretation · 10 Partly supported · 8 Supported · 8 Own method · 7 No basis given · 6 No full text of the sources · 3 Sources not found · 2 Couldn’t confirm · 1 Not checked yet · accuracy not yet measured
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“and is not reported in the gnomAD, a large scale human genome sequence database10”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Could not verifycites [10] Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016). sourceExperimental — accuracy not yet measured
The Article reSeArcH and ExAC data release sections describe a large human exome-variant database, but identify it as ExAC, not gnomAD. The substitution is not specified in the claim, and no passage in our copy establishes whether it is reported in gnomAD (searched: gnomAD, substitution, and database descriptions). (LLM, conf=0.74)
plain- Asserted: passes — The authors put it forward as true.
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- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“This miR-140-null phenotype included mildly advanced terminal differentiation of growth plate chondrocytes of developing bones6,17.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Supportedcites [6] Nakamura, Y., Inloes, J. B., Katagiri, T. & Kobayashi, T. Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling. Mol. Cell. Biol. 31, 3019–3028 (2011). source
In the section “Mir140-null mice show defects in endochondral bone growth,” the paper reports mild acceleration of chondrocyte differentiation. It also reports enlarged hypertrophic regions in developing talus and tibia bones, consistent with earlier terminal differentiation. (LLM, conf=0.91)
- Supportedcites [17] Papaioannou, G. et al. MicroRNA-140 provides robustness to the regulation of hypertrophic chondrocyte differentiation by the PTHrP-HDAC4 pathway. J. Bone Miner. Res. 30, 1044–1052 (2015). source
The Introduction states that miR-140 deficiency accelerates the differentiation of proliferating growth-plate chondrocytes into hypertrophic chondrocytes, while the overall effect is relatively mild. The Results also report accelerated chondrocyte hypertrophy in developing Mir140-null bones. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“loss of miR-140, encoded by Mir140, in mice leads to short stature and craniofacial abnormalities6,16”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Supportedcites [6] Nakamura, Y., Inloes, J. B., Katagiri, T. & Kobayashi, T. Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling. Mol. Cell. Biol. 31, 3019–3028 (2011). source
The Abstract states that loss of Mir140 in mice results in dwarfism and craniofacial deformities. The section “Mir140-null mice show defects in endochondral bone growth” reports impaired growth, shorter long bones, and reduced longitudinal growth of the skull. No page numbers are provided in our copy. (LLM, conf=0.95)
- Supportedcites [16] Miyaki, S. et al. MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev. 24, 1173–1185 (2010). source
The 'Targeted deletion of cartilage-specific miR-140' section reports that mice lacking miR-140 developed short stature and craniofacial deformities after birth (Fig. 2B–E). It also confirms that miR-140 was absent in the knockout mice. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, previously reported YBX1-stabilized transcripts were preferentially repressed in miR-140G/G and miR-140G/+ chondrocytes as compared with miR-140−/− chondrocytes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Supportedcites [34] Goodarzi, H. et al. Endogenous tRNA-derived fragments suppress breast cancer progression via ybx1 displacement. Cell 161, 790–802 (2015). source
The Results sections on competitive tRF binding and target-specific validation report YBX1-bound transcripts whose stability depends on YBX1, supporting the citation's identification of previously reported YBX1-stabilized transcripts. The comparison among miR-140 chondrocytes is the citing authors' finding, not a result attributed to this source. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
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The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“An extended search in copy number variation (CNV) databases regarding human phenotypes associated with CNVs involving the MIR140 gene revealed a single individual with heterozygous 1.1Mb deletion with isolated Arnold-Chiari malformation41.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Identification of the MIR140 mutation
What the sources say
- Could not verifycites [41] Kaminsky, E. B. et al. An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet. Med. 13, 777–784 (2011). sourceExperimental — accuracy not yet measured
The Results section (CNV Characterization; page unavailable) describes aggregate CNV findings, not an individual with the claimed phenotype. Searches of our copy for MIR140, a 1.1 Mb deletion, and Arnold-Chiari malformation found no passage addressing the claimed case. (LLM, conf=0.76)
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This hypothesis is supported by the binding of YBX1 to several miR-140-5p-G target genes in a previously reported YBX1 individual nucleotide resolution crosslinking and immunoprecipitation (iCLIP) dataset”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Partly supportedcites [32] Wu, S. L. et al. Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme. Nucleic Acids Res. 43, 8516–8528 (2015). sourceExperimental — accuracy not yet measured
The Results ('Genome-wide mapping of YB-1-RNA interactions by iCLIP-seq'; page unavailable) identify this paper as a source of YBX1 iCLIP binding data, and the Discussion says its binding sites are enriched in coding genes. Our copy does not identify several miR-140-5p-G target genes as bound by YBX1, so it supports the dataset attribution but not that specific overlap. (LLM, conf=0.82)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The coding region of Hif1a that encodes a master transcription factor controlling hypoxic response27 contains a conserved sequence complementary to the miR-140-5p-G seed sequence.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Supportedcites [27] Wan, C. et al. Role of HIF-1α in skeletal development. Ann. N. Y. Acad. Sci. 1192, 322–326 (2010). source
Citation 27 is attached to the description of Hif1a as encoding a transcription factor that controls the hypoxic response, not to the sentence’s claim about a miR-140-5p-G seed match. The paper’s “hypoxia-inducible factor pathway” section describes HIF as a transcription factor that mediates adaptation to oxygen and identifies HIF-1α as a subunit. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Computational analysis suggested that the miR-140-5p-G seed in the Ago2 complex and the RBP, Ybx1 (also known as YB-1), potentially compete for the same RNA binding sites”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Could not verifycites [30] Ray, D. et al. A compendium of RNA-binding motifs for decoding gene regulation. Nature 499, 172–177 (2013). sourceExperimental — accuracy not yet measured
The Large-scale analysis of RBPs section describes computational analysis of RBP binding motifs, but does not address competition between Ybx1 and an Ago2-bound microRNA. Searches for YBX1, miR-140-5p, and overlapping Ago2/RBP binding sites found no passage supporting the specific claim. (LLM, conf=0.76)
- Partly supportedcites [31] Wei, W. J. et al. YB-1 binds to CAUC motifs and stimulates exon inclusion by enhancing the recruitment of U2AF to weak polypyrimidine tracts. Nucleic Acids Res. 40, 8622–8636 (2012). sourceExperimental — accuracy not yet measured
The Results section (page unavailable) identifies CAUC and CACC as high-affinity RNA-binding motifs for YB-1, supporting the premise that YB-1 binds specific RNA sites. The paper does not report a miR-140-5p-G seed, an Ago2 complex, or computational evidence that either competes with YB-1 for the same sites. (LLM, conf=0.84)
- Could not verifycites [32] Wu, S. L. et al. Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme. Nucleic Acids Res. 43, 8516–8528 (2015). sourceExperimental — accuracy not yet measured
The Results section describes YB-1 binding to RNA and blocking DGCR8 and Dicer loading onto miR-29b-2 precursors. Our copy does not address computationally predicted competition between YB-1 and an Ago2-bound miR-140-5p-G seed for the same binding sites (searched: miR-140-5p-G, Ago2, and competition). (LLM, conf=0.76)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The miR-140-5p-G targets include many genes important for skeletal development and homeostasis, including Loxl3, Btg1, and Trps1, and genes associated with various metabolic pathways”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Partly supportedcites [22] Zhang, J. et al. Loss of lysyl oxidase-like 3 causes cleft palate and spinal deformity in mice. Hum. Mol. Genet. 24, 6174–6185 (2015). sourceExperimental — accuracy not yet measured
The Results section and the supplied Abstract (page not provided) show that loss of Loxl3 disrupts palate and vertebral development in mice, supporting its relevance to skeletal development. The paper does not identify Loxl3, Btg1, or Trps1 as miR-140-5p-G targets, or address the claimed metabolic-pathway targets; searches for those terms found no supporting passage. (LLM, conf=0.86)
- Partly supportedcites [23] Tijchon, E. et al. Targeted deletion of btg1 and btg2 results in homeotic transformation of the axial skeleton. PLoS ONE 10, e0131481 (2015). sourceExperimental — accuracy not yet measured
The Discussion (page not available in our copy) says Btg1 and Btg2 play an important role in vertebral patterning, supporting Btg1’s relevance to skeletal development. The paper does not establish that Btg1, Loxl3, or Trps1 are miR-140-5p-G targets, or address the claimed metabolic-pathway targets. (LLM, conf=0.88)
- Partly supportedcites [24] Napierala, D. et al. Uncoupling of chondrocyte differentiation and perichondrial mineralization underlies the skeletal dysplasia in tricho-rhino-phalangeal syndrome. Hum. Mol. Genet. 17, 2244–2254 (2008). sourceExperimental — accuracy not yet measured
The paper’s opening summary (p. 1) links Trps1 to skeletal dysplasia and bone development, supporting its identification as a gene important to the skeleton. Neither that passage nor the retrieved passages on Trps1 and Runx2 (pp. 5–6) identify miR-140-5p-G targets, Loxl3 or Btg1, or genes associated with metabolic pathways. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, gene set enrichment analysis (GSEA) revealed that the hypoxia pathway is impaired in miR-140G/G, but not in miR-140−/− chondrocytes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Supportedcites [25] Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005). source
The Abstract identifies this paper as the work that developed gene set enrichment analysis (GSEA), supporting its citation for the method used. The reported finding about miR-140 chondrocytes is the citing authors’ result, not a finding attributed to this source. (LLM, conf=0.90)
- Could not verifycites [26] Merico, D., Isserlin, R., Stueker, O., Emili, A. & Bader, G. D. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS ONE 5, e13984 (2010). sourceExperimental — accuracy not yet measured
The Materials and Methods section describes GSEA of breast-cancer-cell data, while the Results section discusses gene sets in early-onset colon cancer; no page numbers are available in our copy. Searches for miR-140 chondrocytes and hypoxia-pathway impairment found no passage addressing the claimed comparison between miR-140G/G and miR-140−/− chondrocytes. (LLM, conf=0.76)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“and delayed cartilage maturation of the larynx, trachea, and anterior ribs”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“These bone abnormalities of miR-140G/G and miR-140G/+ mice are consistent at all analyzed ages from P7 to P56 when compared to wild-type mice”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we describe a neomorphic seed region mutation in the chondrocyte-specific, super-enhancer-associated MIR140 encoding microRNA-140 (miR-140) in a novel autosomal dominant human skeletal dysplasia.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Minor changes in Dicer processing sites and miRNA strand choice were also observed”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MIR140 is associated with a chondrocyte-specific super-enhancer both in humans and mice”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-140G/G and miR-140G/+ mice showed mildly flat vertebral bodies”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The proximal tibial growth plate also showed an expansion of the resting zone in miR-140G/G and miR-140G/+ mice”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“A novel skeletal dysplasia was identified in two unrelated families in a project for molecular diagnosis of ultra-rare congenital skeletal disorders”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plainn = 2- Asserted: passes — The authors put it forward as true.
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In the paper
“Furthermore, the mutant miR-140-5p seed competes with the conserved RNA-binding protein Ybx1 for overlapping binding sites.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Whole genome sequencing (WGS) identified the same heterozygous nucleotide substitution (chr16:g.69967007A>G (hg19), MIR140:NR_029681.1:n.24A>G) in P1 and P2”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Both the miR-140 A>G mutation and miR-140 deletion caused derepression of conserved 8mer target genes for wild-type miR-140-5p and to a lesser extent for miR-140-3p species”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Small RNA sequencing analysis in mouse chondrocytes revealed that the miR-140 A>G mutation yields slightly greater amounts of the mutant miR-140-5p (miR-140-5p-G) than wild-type miR-140-5p”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Herein, we describe a novel skeletal dysplasia caused by a single nucleotide substitution in the MIR140 gene and the underlying mechanism.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“only miR-140G/G and miR-140G/+ mice showed delayed secondary ossification of tubular and carpal bones”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The spondylar and epiphyseal abnormalities evolved into premature spondylosis and degenerative joint disease in adulthood, respectively.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirectn = 3- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Expression levels of genes within the neighborhood of the miR-140 gene locus were not largely affected”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The same single nucleotide substitution occurred de novo in P1 and P3”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In chondrocytes, the mutation causes widespread derepression of wild-type miR-140-5p targets and repression of mutant miR-140-5p targets”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and co-segregated with the skeletal dysplasia phenotype in Family 1”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“decreased expression of Col10a1, a maturation marker for hypertrophic chondrocytes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We did not find an increased number of apoptotic cells in the growth plate of miR-140G/G mice”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This substitution is located at the first nucleotide of the seed sequence of the highly conserved microRNA (miRNA), miR-140-5p, encoded by MIR140”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Micro-CT analysis showed severely decreased epiphyseal mineralization in miR-140G/G mice”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Principle component analysis and hierarchical clustering analysis of the RNA-seq data clearly distinguished miR-140G/G and miR-140G/+ mice from miR-140−/− and wild-type mice”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“while decreasing two miR-140-3p species (3p.1 and 3p.2)”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The proliferation rate of tibial growth plate chondrocytes was not significantly different among miR-140G/G, miR-140G/+, and wild-type mice”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In chondrocytes, the mutation causes widespread derepression of wild-type miR-140-5p targets and repression of mutant miR-140-5p targets”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ago2 seCLIP analysis revealed crosslink site-centric enrichment of hexamer sequences complementary to the seed sequences of wild-type miR-140-5p and miR-140-5p-G in Ago2 seCLIP clusters in wild-type and miR-140G/G chondrocytes, respectively”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“with a concomitant decrease in collagen crosslinking in the rib cartilage”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, the widespread suppression of predicted miR-140-5p-G targets is only observed in miR-140G/G and miR-140G/+ chondrocytes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It also demonstrated crosslink site-centric enrichment of a hexamer sequence (“ACCACC”) complementary to the seed of miR-140-5p-G”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, miR-140-5p-G Ago2 seCLIP target genes with Ybx1 binding in the 3′ UTR showed stronger repression in mutant chondrocytes than those without Ybx1 binding”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accordingly, wild-type and the mutant miR-140-5p showed similar target site efficiencies by TargetScan prediction”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hif1a protein expression was reduced in miR-140G/G chondrocytes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, expression of several extracellular matrix genes including Col10a1 decreased in miR-140G/G and miR-140G/+ chondrocytes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, a single-cell 3′ UTR reporter assay of several miR-140-5p-G target genes demonstrated that suppressive effects by miR-140-5p-G were dampened by Ybx1 inhibition”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No individuals with short stature and heterozygous deletions of greater than 2Mb size including the MIR140 gene were reported in the CNV databases”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Identification of the MIR140 mutation
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, systematic RBP motif analysis suggested that Ybx1 activity was selectively suppressed in miR-140G/G but not in miR-140−/− chondrocytes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No potential disease causing variants were found in the protein coding genes.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Identification of the MIR140 mutation
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This effect was not apparent for the target sites in coding sequences (CDS)”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They did not show any of endocrine abnormalities seen in acrodysostosis such as hypocalcemia, hyperphosphatemia, elevated levels of parathyroid hormone (PTH) and/or thyroid stimulating hormone (TSH), and decreased insulin-like growth factor 1 (IGF-1).”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Clinical diagnosis of spondyloepiphyseal dysplasia (SED) MIR140 type Nishimura
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the presented patients did not have mutations in the PDE4D and PRKAR1A genes known to be associated with acrodysostosis.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Clinical diagnosis of spondyloepiphyseal dysplasia (SED) MIR140 type Nishimura
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“mRNA expression of Hif1a and Hif1a-regulated molecules including lysyl oxidases, essential for collagen crosslinking, significantly decreased in miR-140G/G chondrocytes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The target sites of miR-140-5p-G are less conserved than those of wild-type miR-140 species.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The miR-140 locus is associated with high ChIP-seq signals of H3K27Ac and Sox9 in mouse chondrocytes.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Delay in chondrocyte mineralization in the rib cartilage is observed in miR-140G/G and miR-140G/+ mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Deregulation of miR-140-5p-G targets in miR-140 mutant chondrocytes.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We observed that multiple conserved miR-140-5p-G target genes were bound by YBX1 in the YBX1 iCLIP dataset.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
What the sources say
- Not matchedcites Ref. 32
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“High CWCS was associated with stronger target gene regulation for both miR-140-5p-G and miR-140-5p-WT”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Delayed maturation of the proximal tibial epiphysis in P56-old mutant mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plainn = 6- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A close view of the larynx and vocal folds shows dorsal narrowing of the subglottic region (c).”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Validation of the Hif1a target site.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Vertebral bodies of miR-140G/G mice are smaller compared with miR-140G/+, miR-140+/+, and miR-140−/− mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Significant changes of other miRNAs are not observed.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Note that Ybx1 protein expression levels normalized to those of Actb did not differ between wild-type and mutant chondrocytes.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Apoptotic cells were not observed in the growth plate of miR-140G/G or miR-140+/+ mice (f).”
- Also stated in: § Extended Data · plain
“there were no TUNEL-positive cells in the growth plate cartilage in both miR-140+/+ and miR-140G/G mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Extended Data · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-140G/G mice are smaller.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Decreased expression of Col10a1 is observed in miR-140G/G and miR-140G/+ mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among three significantly suppressed motifs in miR-140-G homozygous cells (SRSF10, YBX1, and SRSF9), only the YBX1 RBP motif gene set was selectively suppressed in miR-140-G homozygous but not miR-140-null cells.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reduced laryngeal contraction is observed during expiration (b).”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Measurements of tibial growth plates of P56 mice show significant expansions in miR-140G/G and miR-140G/+ mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaincorrelationaln = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reduced collagen crosslinking in miR-140G/G rib cartilage cells.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaindirectn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cartilage mineralization is absent or severely impaired in miR-140G/+ and miR-140G/G mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our study presents the first case of a pathogenic gain-of-function miRNA mutation”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Neomorphic (gain-of-new-function) mutations in miRNAs due to nucleotide substitutions have not been reported.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This finding may explain the potent target repression and robust in vivo effect by this mutant miRNA even in the absence of evolutionary selection of miRNA-target RNA interactions”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the delayed skeletal maturation observed in humans and mice with the miR-140 substitution suggests a common pathogenic mechanism.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“and provides molecular insight into neomorphic actions of emerging and/or mutant miRNAs.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
plainSingle case- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“miR-140-5p and miR-140-3p (collectively miR-140) are abundantly and relatively specifically expressed in chondrocytes14,15”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Not checked — no full text of the sourcecites [14] Wienholds, E. et al. MicroRNA expression in zebrafish embryonic development. Science 309, 310–311 (2005). source
- Not checked — no full text of the sourcecites [15] Tuddenham, L. et al. The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells. FEBS Lett. 580, 4214–4217 (2006). source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“These alterations in genes important for cartilage and chondrocyte functions may contribute to the skeletal abnormalities of miR-140G/G and miR-140G/+ mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting that the miR-140-5p-G-target interaction follows the molecular rules of conventional miRNA targeting.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This finding suggests that sequence-dependent crosstalks with RBPs may confer extended biological properties to miRNAs and other types of regulatory RNAs.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such sequence-dependent competition between a miRNA seed and an RBP would add a new mechanism of transcript regulation.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This trend was not observed for the CDS seCLIP clusters (Fig. 4g), suggesting a predominant competition between miR-140-5pG and Ybx1 in 3′ UTRs.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedged- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this suggests that miR-140-G directly suppresses Hif1a.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“and thus suggests the possibility that some of currently unresolved congenital disorders may be caused by neomorphic miRNA mutations.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“supporting the hypothesis that the heterozygous nucleotide substitution (chr16:g.69967007A>G (hg19), MIR140:NR_029681.1:n.24A>G) is a neomorphic mutation.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Identification of the MIR140 mutation
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“This result suggests that haploinsufficiency of MIR140 does not lead to skeletal abnormalities in humans”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Identification of the MIR140 mutation
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“These observations collectively suggest that the potent suppressive effect of miR-140-5p-G is partly attributable to the competition against Ybx1, especially in 3′ UTRs, and subsequent suppression of Ybx1 activity.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Ago2 prefers strands with 5′-uridine or 5′-adenosine and thermodynamically unstable 5′-ends.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
What the sources say
- Not matchedcites Ref. 20
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“consistent with the increase in miR-140-5p and decrease in miR-140-3p in chondrocytes from miR-140G/+ and miR-140G/G mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Small RNA sequencing and analysis
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Ago2 prefers strands with 5′-uridine or 5′-adenosine and thermodynamically unstable 5′-ends.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Small RNA sequencing and analysis
What the sources say
- Not checked — no full text of the sourcecites [20] Suzuki, H. I. et al. Small-RNA asymmetry is directly driven by mammalian Argonautes. Nat. Struct. Mol. Biol. 22, 512–521 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Selection of a single mature miRNA strand from miRNA duplex is determined by combination of 5′-end nucleotide identity and thermodynamic asymmetry of miRNA duplex termini20.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Small RNA sequencing and analysis
What the sources say
- Not checked — no full text of the sourcecites [20] Suzuki, H. I. et al. Small-RNA asymmetry is directly driven by mammalian Argonautes. Nat. Struct. Mol. Biol. 22, 512–521 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This mechanistically explains abundant expression of miR-140-3p compared with miR-140-5p in chondrocytes.”
- Also stated in: § Extended Data · boosted
“This mechanistically explains abundant expression of miR-140-3p compared with miR-140-5p in chondrocytes.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Small RNA sequencing and analysis
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Extended Data · boosted
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“majority of intronic clusters was considered to be non-specific due to the low sensitivity of seCLIP for small starting materials like primary chondrocytes.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > seCLIP analysis
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The consistency of the phenotype was confirmed in two lines.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Mice
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The A>G substitution is predicted to destabilize the 5′-end of the 5p arm and thus to increase the 5p/3p ratio for both 5p/3p.1 and 5p/3p.2 duplexes”
- Also stated in: § Extended Data · plain
“Note that the A>G substitution is predicted to destabilize the 5′-end of the 5p arm and thus to increase the 5p/3p ratio for both 5p/3p.1 and 5p/3p.2 duplexes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Small RNA sequencing and analysis
What the sources say
- Not checked — no full text of the sourcecites [20] Suzuki, H. I. et al. Small-RNA asymmetry is directly driven by mammalian Argonautes. Nat. Struct. Mol. Biol. 22, 512–521 (2015). source
- Not matchedcites Ref. 20
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Extended Data · plain
- Probably not a substantial claim. 36
- It may state two separate claims as one. 32
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Heterozygous loss-of-function point mutations of miRNA genes are associated with several human congenital disorders1–5”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Not checked — no full text of the sourcecites [1] Mencia, A. et al. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat. Genet. 41, 609–613 (2009). source
- Partly supportedcites [2] Solda, G. et al. A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing. Hum. Mol. Genet. 21, 577–585 (2012). sourceExperimental — accuracy not yet measured
The Discussion reports a MIR96 point mutation that reduces mature miRNA levels and causes inherited hearing loss. It does not establish an association with several human congenital disorders: the affected family’s hearing loss began between ages 25 and 40, rather than being present at birth. (LLM, conf=0.90)
- Partly supportedcites [3] Hughes, A. E. et al. Mutation altering the miR-184 seed region causes familial keratoconus with cataract. Am. J. Hum. Genet. 89, 628–633 (2011). sourceExperimental — accuracy not yet measured
The main text (page unavailable) identifies a heterozygous point mutation in MIR184 associated with familial keratoconus and early-onset cataract, and reports that the mutant loses a tested miR-184 function. This supports an example within the multiply cited statement, but the paper does not establish that the affected individuals’ condition was congenital: it describes the cataract as early-onset. (LLM, conf=0.83)
- Partly supportedcites [4] Iliff, B. W., Riazuddin, S. A. & Gottsch, J. D. A single-base substitution in the seed region of miR-184 causes EDICT syndrome. Invest. Ophthalmol. Vis. Sci. 53, 348–353 (2012). sourceExperimental — accuracy not yet measured
The Results (page unavailable) identify a heterozygous single-base substitution in miR-184 that segregates with EDICT syndrome, which includes congenital cataract. The Discussion (page unavailable) proposes reduced miR-184 expression or activity as possible mechanisms but does not establish loss of function. This paper provides one example, not evidence for several congenital disorders. (LLM, conf=0.86)
- Partly supportedcites [5] Lechner, J. et al. Mutational analysis of MIR184 in sporadic keratoconus and myopia. Invest. Ophthalmol. Vis. Sci. 54, 5266–5272 (2013). sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) reports two heterozygous MIR184 substitutions in patients with keratoconus and shows that both reduced mature miR-184 expression; it also links a MIR184 mutation to EDICT syndrome, which includes congenital cataract. The Discussion (page unavailable) mentions MIR96 mutations associated with progressive hearing loss, but does not establish that heterozygous loss-of-function mutations across miRNA genes are associated with several congenital disorders. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Mice with the corresponding single nucleotide substitution show skeletal abnormalities similar to those of the patients but distinct from those of miR-140-null mice6.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Partly supportedcites [6] Nakamura, Y., Inloes, J. B., Katagiri, T. & Kobayashi, T. Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling. Mol. Cell. Biol. 31, 3019–3028 (2011). sourceExperimental — accuracy not yet measured
The section ‘Mir140-null mice show defects in endochondral bone growth’ describes skeletal abnormalities in Mir140-null mice. But the paper describes a Mir140 deletion, not mice with the claimed single-nucleotide substitution; our copy does not report patient abnormalities or compare substitution-bearing mice with null mice. (LLM, conf=0.78)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Super-enhancers commonly drive high-level expression of tissue-specific genes, including miRNA genes, with evolutionarily conserved cell type-specific function11–13.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Supportedcites [11] Suzuki, H. I., Young, R. A. & Sharp, P. A. Super-enhancer-mediated RNA processing revealed by integrative microrna network analysis. Cell 168, 1000–1014 e1015 (2017). source
The Results section ‘Super-enhancers mark cell-type-specific and abundant miRNAs’ reports exceedingly high, cell-type-specific expression of super-enhancer-associated miRNAs. ‘Super-enhancer-miRNA network and evolution’ links their targets to tissue-characteristic functions and reports a tissue-dependent pattern suggesting co-evolution; the Introduction also describes the analysis of evolutionary conservation of miRNA networks. The Discussion characterizes super-enhancers more broadly as regulators of cell-identity genes. Page numbers are unavailable in our copy. (LLM, conf=0.86)
- Partly supportedcites [12] Whyte, W. A. et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153, 307–319 (2013). sourceExperimental — accuracy not yet measured
The Results sections on functional attributes and cell identity report higher expression of super-enhancer-associated genes, cell type-specific associations, and an ESC miRNA locus among those genes. The Discussion says these regulatory clusters evolved, but our copy does not establish that their cell type-specific functions are evolutionarily conserved. (LLM, conf=0.87)
- Partly supportedcites [13] Hnisz, D. et al. Super-enhancers in the control of cell identity and disease. Cell 155, 934–947 (2013). sourceExperimental — accuracy not yet measured
The Results section reports that super-enhancers drive high-level expression of associated genes, and the Discussion says those genes tend to have cell type-specific expression and include miRNAs. Our copy does not establish that their cell type-specific function is evolutionarily conserved (pages not provided). (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“We observed that ceRBP effects are widespread in RNAi and contributes to off-target effects and phenotype modulation40.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Supportedcites [40] Suzuki, H. I., Spengler, R. M., Grigelioniene, G., Kobayashi, T. & Sharp, P. A. Deconvolution of seed and RNA-binding protein crosstalk in RNAi-based functional genomics. Nat. Genet. 50, 657–661 (2018). source
The Abstract states that seed-to-RBP crosstalk is widespread, contributes to off-target activity, and affects RNAi performance. It specifically reports widespread contributions to growth-phenotype modulation, supporting the citing sentence's paraphrase. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“YBX1 is a multifunctional RBP that stabilizes mRNAs and regulates RNA splicing33,34.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Not checked — no full text of the sourcecites [33] Lyabin, D. N., Eliseeva, I. A. & Ovchinnikov, L. P. YB-1 protein: functions and regulation. Wiley Interdiscip. Rev. RNA 5, 95–110 (2014). source
- Partly supportedcites [34] Goodarzi, H. et al. Endogenous tRNA-derived fragments suppress breast cancer progression via ybx1 displacement. Cell 161, 790–802 (2015). sourceExperimental — accuracy not yet measured
The Results section describes YBX1 as a multifunctional RNA-binding protein, and the Introduction and Discussion say it stabilizes target transcripts. Our copy does not say that YBX1 regulates RNA splicing; a search for splicing found no supporting passage. Page numbers were not available in the indexed copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Next, Ybx1 seCLIP analysis identified a binding motif similar to the Ybx1 binding motif reported previously30–32”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Could not verifycites [30] Ray, D. et al. A compendium of RNA-binding motifs for decoding gene regulation. Nature 499, 172–177 (2013). sourceExperimental — accuracy not yet measured
The Large-scale analysis of RBPs section describes how the paper derived RNA-binding motifs, but the passages found do not identify a YBX1 motif. Searches for “YBX1,” “YB-1,” and “Y-box binding protein 1” found no passage establishing the specific motif comparison attributed to this source. (LLM, conf=0.72)
- Supportedcites [31] Wei, W. J. et al. YB-1 binds to CAUC motifs and stimulates exon inclusion by enhancing the recruitment of U2AF to weak polypyrimidine tracts. Nucleic Acids Res. 40, 8622–8636 (2012). source
The Results section, “Defining the RNA-binding specificity of YB-1 by SELEX,” reports a YB-1 binding motif with CAUC and CACC variants. The citation supports the previously reported motif; the seCLIP finding is the citing authors’ own analysis, not a result attributed to this paper. (LLM, conf=0.92)
- Supportedcites [32] Wu, S. L. et al. Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme. Nucleic Acids Res. 43, 8516–8528 (2015). source
The Results section (‘In vivo RNA binding specificity of YB-1’) reports a YB-1 binding consensus of UYAUC and says it closely resembles a previously determined in vitro SELEX motif. The cited paper used iCLIP, while seCLIP describes the citing authors’ analysis, not a method attributed to this source. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Besides gene dosage abnormalities37,38, single nucleotide substitutions in two miRNA genes have been identified in human diseases: MIR96 mutations in autosomal dominant deafness 50 (#613704) and MIR184 mutations in EDICT syndrome (#614303) and familial and sporadic cases of keratoconus1–5,39.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Not checked — no full text of the sourcecites [1] Mencia, A. et al. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat. Genet. 41, 609–613 (2009). source
- Partly supportedcites [2] Solda, G. et al. A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing. Hum. Mol. Genet. 21, 577–585 (2012). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [3] Hughes, A. E. et al. Mutation altering the miR-184 seed region causes familial keratoconus with cataract. Am. J. Hum. Genet. 89, 628–633 (2011). source
This paper is one of several citations attached to the MIR184 clause; its contribution is the familial keratoconus case. The paper’s opening summary reports a MIR184 seed-region mutation responsible for familial severe keratoconus with early-onset cataract (opening section; page unavailable). (LLM, conf=0.90)
- Partly supportedcites [4] Iliff, B. W., Riazuddin, S. A. & Gottsch, J. D. A single-base substitution in the seed region of miR-184 causes EDICT syndrome. Invest. Ophthalmol. Vis. Sci. 53, 348–353 (2012). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [5] Lechner, J. et al. Mutational analysis of MIR184 in sporadic keratoconus and myopia. Invest. Ophthalmol. Vis. Sci. 54, 5266–5272 (2013). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [39] Lewis, M. A. et al. An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice. Nat. Genet. 41, 614–618 (2009). sourceExperimental — accuracy not yet measured
The paper’s discussion reports two single-base changes in the miR-96 seed region in humans with progressive hearing loss, supporting the MIR96 portion of the claim. It does not identify autosomal dominant deafness 50 or address MIR184, EDICT syndrome, or keratoconus. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Gene regulation by conserved miRNAs has a significant impact on 3′ UTR evolution, and evolutionarily maintained target sites mediate actions of miRNAs more effectively than non-conserved target sites28.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Supportedcites [28] Grimson, A. et al. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol. Cell 27, 91–105 (2007). source
The Introduction reports that more than 200 messages, on average, are under selective pressure to maintain sites for each highly conserved mammalian miRNA family, supporting an impact on 3′ UTR evolution. In the paper’s discussion of its quantitative efficacy model (page unavailable), conserved sites were somewhat more effective than nonconserved sites with the same score. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“miR-140-null mice were previously described6.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Mice
What the sources say
- Supportedcites [6] Nakamura, Y., Inloes, J. B., Katagiri, T. & Kobayashi, T. Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling. Mol. Cell. Biol. 31, 3019–3028 (2011). source
The section “Generation of Mir140-null mice” describes how the authors produced the mice. The section “Mir140-null mice show defects in endochondral bone growth” confirms that mice lacking Mir140 were generated by gene targeting. This paper therefore describes the mice identified by the citation. (LLM, conf=0.95)
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In the paper
“Mouse H3K27Ac and Sox9 ChIP-seq profiles were previously described51.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Super-enhancer analysis
What the sources say
- Supportedcites [51] Ohba, S., He, X., Hojo, H. & McMahon, A. P. Distinct transcriptional programs underlie Sox9 regulation of the mammalian chondrocyte. Cell Rep. 12, 229–243 (2015). source
The Results section (Identification of Sox9 Class I targets; page unavailable) describes ChIP-seq datasets from mouse rib chondrocytes and reports a Sox9 ChIP-seq profile. The Results section on Class II targets also describes H3K27Ac peaks flanking Sox9-bound regions, supporting the identification of the previously described profiles. (LLM, conf=0.90)
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In the paper
“Although miR-140G/G and miR-140−/− mice were smaller and had shorter noses than wild-type littermates”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“Clinical features of the skeletal dysplasia included disproportionate short stature with short limbs, small hands and feet, and midface hypoplasia with small nose.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“The radiological hallmarks were mild spondylar dysplasia, delayed epiphyseal ossification of the hip and knee, and severe brachydactyly with cone shaped phalangeal epiphyses”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“This mutant miRNA gene yields abundant mutant miR-140-5p expression without miRNA-processing defects.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“The basal skull growth plate was wider due to the increased length of all layers of chondrocytes in miR-140G/G and miR-140G/+ mice, whereas miR-140−/− mice showed no significant changes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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“P1 and P2 also suffered from frequent respiratory infections with prolonged cough and inspiratory stridor.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“All three affected individuals had normal intelligence, dentition, hearing, visual acuity, and basic blood tests.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“P1 had a narrow larynx likely due to floppy cartilage”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“Target sites of miR-140-5p-G seldom overlapped with those of wild-type miR-140 species (wild-type 5p, 3p.1, and 3p.2) and were less conserved than those of wild-type miR-140 species”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“Out of 61 mice embryos injected with the guide RNA, repair template and Cas9, 11 mice were positive for the knock-in mutation.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Mice
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In the paper
“Screening P1, P2, and P3 for possible disease causing variants in 378 known skeletal dysplasia genes using WGS data, and screening P2 for gene dose abnormalities of the above mentioned skeletal dysplasia genes using custom-designed comparative genome hybridization analysis was all negative (data not shown), excluding involvement of these genes in the skeletal dysplasia phenotype of our patients.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Identification of the MIR140 mutation
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In the paper
“All of these mice were compound heterozygous with one allele mutated as desired and the other with various size insertion-deletion mutations.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Mice
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In the paper
“In contrast, the miR-140 mutation found in this study affected the same nucleotide in both families and resulted in gain of a new function as well as loss of the original function, as shown by the transcriptome analysis revealing repression of new target genes and derepression of original targets.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“This suppressive effect of miR-140-5p-G is particularly strong for 8mer target sites (Extended Data Fig. 6b) and correlates with the predicted miRNA target efficiency”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“A 3′ UTR reporter assay, using minimal target sequences and endogenous 3′ UTR sequences, confirmed that miR-140-5p-G and wild-type miR-140-5p target their respective predicted 8mer target sites with similar strengths, and validated the efficiency of target sites in several genes, respectively”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“Accordingly, genes with the identified 3′ UTR target sites of miR-140-5p-G were downregulated only in miR-140G/G and miR-140G/+ chondrocytes, while genes with wild-type miR-140-5p target sites were upregulated in both miR-140-null and miR-140 mutant chondrocytes”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“White arrow indicates apoptotic cells associated with blood vessels invaded into the epiphysis of wild type mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
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In the paper
“The right arytenoid cartilage is enlarged with redundant soft tissues and it prolapses antero-medially over the larynx during inspiration (a).”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
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In the paper
“miR-140-5p-WT and miR-140-5p-G show similar and higher predicted target site efficiency than miR-140-3p.1 and miR-140-3p.2.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Fiberscopy findings in P1, 44 years of age, consistent with laryngomalacia.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“The second nucleotide in miR-140-5p is conserved from human to Australian ghostshark (indicated by a black arrow).”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
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In the paper
“The pathogenic variant in MIR140 (chr16:g.69967007A>G) (indicated by black arrows) in whole genome sequencing and exome sequencing data (left and right panels), and its Sanger sequencing confirmation (middle panel) in individuals P1, 2, and 3 as in Fig. 1.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
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In the paper
“Note that miR-140-5p and miR-140-3p are highly abundant miRNAs in chondrocytes, reflecting super-enhancer-mediated high transcriptional activity.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
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In the paper
“Since we found no phenotypic differences between males and females, males and females were not discriminated for the analysis.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Skeletal preparation and histology
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In the paper
“consistent with the increase in miR-140-5p and decrease in miR-140-3p in chondrocytes from miR-140G/+ and miR-140G/G mice.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
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In the paper
“enrichment of miRNA motifs and Ybx1 motifs was not observed in intronic clusters (Extended Data Fig. 9b and 10b)”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > seCLIP analysis
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In the paper
“Mutations in approximately 400 different genes are currently known to cause congenital skeletal diseases9”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Not checked — no full text of the sourcecites [9] Bonafe, L. et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am. J. Med. Genet. A 167A, 2869–2892 (2015). source
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In the paper
“These data indicate that the A>G mutation did not compromise miRNA processing and yielded abundant expression of miR-140-5p-G from primary miR-140 transcripts of which transcription is strongly activated by a super-enhancer in chondrocytes.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“and are highly consistent with the skeletal dysplasia features of the patients, presenting with delayed secondary ossification, mild platyspondyly, small epiphyses, and scaphocephaly.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“indicating that the mutation produces both loss-of-function and gain-of-function effects.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“Taken together, these differences in phenotype between miR-140G/G and miR-140−/− mice, and delayed epiphyseal maturation in humans, indicate that this single-base substitution causes a neomorphic, and not just loss-of-function, effect.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“However, these mutations, occurring at multiple different nucleotides of single miRNAs, are thought to primarily cause loss of function”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“the disease phenotype may be at least partially explained by potential competition with the RBP, Ybx1, and by the super-enhancer-driven high-level miRNA expression”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“a neomorphic mutant miRNA would need to target a biologically important regulatory network in order to produce a disease phenotype.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“multiple RNA binding proteins (RBPs) are reported to modulate miRNA function29”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Not checked — no full text of the sourcecites [29] van Kouwenhove, M., Kedde, M. & Agami, R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat. Rev. Cancer 11, 644–656 (2011). source
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In the paper
“Overall, the present study expands our knowledge on how mutations in miRNAs contribute to human disease development”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“suggesting that miR-140-5p exerts greater target repression than miR-140-3p even though the latter is more abundant.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
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In the paper
“In addition, given the expansion of miRNA genes in vertebrates7,8, the molecular mechanism revealed in this present study also has broader implications in understanding how function of new miRNA genes might evolve in humans.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Abstract
What the sources say
- Not checked — no full text of the sourcecites [7] Chen, K. & Rajewsky, N. The evolution of gene regulation by transcription factors and microRNAs. Nat. Rev. Genet. 8, 93–103 (2007). source
- Not checked — no full text of the sourcecites [8] Berezikov, E. Evolution of microRNA diversity and regulation in animals. Nat. Rev. Genet. 12, 846–860 (2011). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“She had normal bone density for the age, which suggests that the heterozygous MIR140 mutation in humans does not lead to bone mass abnormalities.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Clinical diagnosis of spondyloepiphyseal dysplasia (SED) MIR140 type Nishimura
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In the paper
“This substitution creates a novel restriction enzyme site (Msp I; CCGG).”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Mice
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In the paper
“The sample size was estimated based on our prior experience of similar sets of experiments.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Luciferase reporter assay
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“HEK293T cells are tested for mycoplasma contamination.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Luciferase reporter assay
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Micro-CT analysis was performed in a blinded manner with all mice assigned to coded sample numbers.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Micro-CT analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that miR-140-5p-G follows mechanisms of conventional miRNA targeting as well as other endogenous miRNAs.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Note that miR-140-5p and miR-140-3p are highly abundant miRNAs in chondrocytes, reflecting super-enhancer-mediated high transcriptional activity.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The sample size was estimated based on our prior experience of performing similar sets of experiments and the number of examined mice is shown in Supplemental Table 2.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Mice
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“After confirming the absence of additional mutations in the 2 kb region surrounding the Mir140 gene using Sanger sequencing”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Mice
plainn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Each experiment included non-transfection controls.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Single-cell dual fluorescence reporter assay
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Selection of a single mature miRNA strand from miRNA duplex is determined by combination of 5′-end nucleotide identity and thermodynamic asymmetry of miRNA duplex termini (Ref. 20).”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Extended Data
What the sources say
- Not matchedcites Ref. 20
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The PCR amplicon containing the A>G substitution is digested into 98 bp and 119 bp long fragments.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Mice
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We independently repeated the molecular biology experiment at least twice, and all attempts to reproduce the results were successful.”
- Also stated in: § Statistical analysis · plain
“In molecular biology experiments, results are representative of more than two independent and reproducible experiments.”
§ Gain-of-function mutation of microRNA-140 in human skeletal dysplasia > Methods > Luciferase reporter assay
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Also stated in: § Statistical analysis · plain
The paper relies on this without support.
Neomorphic (gain-of-new-function) mutations in miRNAs due to nucleotide substitutions have not been reported.
“but neomorphic (gain-of-new-function) mutations in miRNAs due to nucleotide substitutions have not been reported.”
The paper relies on this without support.
Underlying molecular mechanisms are not elucidated for many congenital skeletal diseases.
“but underlying molecular mechanisms are not elucidated for many of them.”
The paper relies on this without support.
A mutation in the miRNA seed region creates a new repertoire of target genes and the magnitude of such target suppression is typically small.
“Since a mutation in the miRNA seed region creates a new repertoire of target genes and the magnitude of such target suppression is typically small”
Citations
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · cited 2×
“3h, i) 25,26 .”
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · cited 1×
“5.1b) 54 and Cufflinks (2.2.0) 55 .”
InfluentialRobinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · cited 1×
“Filtered reads were mapped to the mm9 genome assembly with bowtie 1.0.1, allowing two mismatches, and further quantitated using miRBase v21 as previously described 52,58 .”
InfluentialModel-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133 · cited 1×
“To investigate the possible disease-causing role of the mutant miR-140, we introduced this single-nucleotide substitution into the mouse genome using the CRISPR-Cas9 technology 18 .”
Cited by
Sorted by citations
Nosology and classification of genetic skeletal disorders: 2019 revision
Mortier, G. R., Cohn, D. H., Cormier‐Daire, V., Hall, C., Krakow, D., Mundlos, S., Nishimura, G., Robertson, S., Sangiorgi, L., Savarirayan, R., et al. (2019) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61366 · Cited by 600
“Interestingly, the current Nosology now includes the first example of pathogenic variants in a miRNA causing a skeletal dysplasia (SED, MIR140 type; group 15) (Grigelioniene et al., 2019).”
BackgroundSelf-citationPrimorac, D., Molnar, V., Rod, E., Jeleč, Ž., Čukelj, F., Matišić, V., Vrdoljak, T., Hudetz, D., Hajsok, H., & Borić, I. (2020) · Genes · doi:10.3390/genes11080854 · Cited by 636
Stranneheim, H., Lagerstedt‐Robinson, K., Magnusson, M., Kvarnung, M., Nilsson, D., Lesko, N., Engvall, M., Anderlid, B., Arnell, H., Johansson, C. B., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00855-5 · Cited by 280
“[55], and MIR140 (skeletal dysplasia) [52].”
Self-citationSystems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis
Matsuyama, H., & Suzuki, H. I. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010132 · Cited by 258
Self-citationCartilage Homeostasis and Osteoarthritis
Fujii, Y., Liu, L., Yagasaki, L., Inotsume, M., Chiba, T., & Asahara, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116316 · Cited by 206
Metadata
- Authors
- Grigelioniene, G., Suzuki, H. I., Taylan, F., Mirzamohammadi, F., Borochowitz, Z. U., Ayturk, U. M., Tzur, S., Horemuzova, E., Lindstrand, A., Weis, M. A., Grigelionis, G., Hammarsjö, A., Marsk, E., Nordgren, A., Nordenskjöld, M., Eyre, D. R., Warman, M. L., Nishimura, G., Sharp, P. A., & Kobayashi, T.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Karolinska Institutet (SE)
- Harvard University (US)
- Technion – Israel Institute of Technology (IL)
- Boston Children's Hospital (US)
- Rambam Health Care Campus (IL)
- Karolinska University Hospital (SE)
- University of Washington (US)
- Saitama Medical University Hospital (JP)
- Corresponding author
- Kobayashi, Tatsuya
- ORCID
- Venue
- Nature Medicine
- Published
- 2019-02-25
- Volume
- 25
- Issue
- 4
- Pages
- 583-590
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6622181
- OpenAlex
- W2917129046
- Semantic Scholar
- dffcad30f105f92c7952744d74b10b64d6c8ec7f
- Cited by
- 103
- References
- 65
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 10 · 2023: 18 · 2022: 15 · 2021: 13 · 2020: 22 · 2019: 8
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- Eli Lilly and Company
- Massachusetts Institute of Technology (P30-CA14051)
- Dana-Farber Cancer Institute
- Uehara Memorial Foundation (NIH P30)
- European Society for Paediatric Endocrinology
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (P30-CA14051)
- Karolinska Institutet
- Stockholms Läns Landsting (20150143)
- Vetenskapsrådet (2018-03046, 2018-)
- Svenska Läkaresällskapet
- Stiftelsen Samariten
- Science for Life Laboratory
- National Institutes of Health (P30-AR066261, GM034277, AR066261, R01-GM034277)
- Uppsala Multidisciplinary Center for Advanced Computational Science
- National Cancer Institute (P01 CA 042063, R01CA133404, CA14051, P30CA014051, P30-CA-14051)
- National Institute of General Medical Sciences (R01 GM034277)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30 AR066261, R01AR056645)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- microRNA-140, gain-of-function mutations, neomorphic mutations, skeletal dysplasia, chondrocytes, YB-1, post-transcriptional regulation, super-enhancers, mouse model
- MeSH terms
- Gain of Function Mutation, Animals, Base Sequence, Bone Diseases, Developmental, Female, Homozygote, Humans, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Pedigree, Phenotype, Chondrocytes, MicroRNAs, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-20, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-20 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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