The DOI matches its Crossref record; 67 of the 68 references it cites were found in a registry or an index; 4 of the 39 sources its claims cite were checked for support.
A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements
Open accessAbstract
While hundreds of novel microRNA (miRNA) genes have been discovered in the last few years alone, the origin and evolution of these non-coding regulatory sequences remain largely obscure. In this report, we demonstrate that members of a recently discovered family of human miRNA genes, hsa-mir-548, are derived from Made1 transposable elements. Made1 elements are short miniature inverted-repeat transposable elements (MITEs), which consist of two 37 base pair (bp) terminal inverted repeats that flank 6 bp of internal sequence. Thus, Made1 elements are nearly perfect palindromes, and when expressed as RNA they form highly stable hairpin loops. Apparently, these Made1-related structures are recognized by the RNA interference enzymatic machinery and processed to form 22 bp mature miRNA sequences. Consistent with their origin from MITEs, hsa-mir-548 genes are primate-specific and have many potential paralogs in the human genome. There are more than 3,500 putative hsa-mir-548 target genes; analysis of their expression profiles and functional affinities suggests cancer-related regulatory roles for hsa-mir-548. Taken together, the characteristics of Made1 elements, and MITEs in general, point to a specific mechanism for the generation of numerous small regulatory RNAs and target sites throughout the genome. The evolutionary lineage-specific nature of MITEs could also provide for the generation of novel regulatory phenotypes related to species diversification. Finally, we propose that MITEs may represent an evolutionary link between siRNAs and miRNAs.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
The paper reports that seven human hsa-mir-548 miRNA genes are derived from Made1 miniature inverted-repeat transposable elements, whose palindromic terminal inverted repeats can form hairpins processed into 22-nt mature miRNAs. It further predicts thousands of hsa-mir-548 target genes and links the family to cancer-related regulatory roles.
Key findings
- Seven closely related hsa-mir-548 miRNA genes were co-located with Made1 elements; Made1 elements are 80 bp long, with two 37 bp terminal inverted repeats flanking 6 bp of internal sequence, and the mature hsa-mir-548 miRNAs are 22 nt.
- Made1 sequences are expressed: 141 human ESTs matched the Made1 query with >80% similarity over >80% of the element, and hsa-mir-548 genes are primate-specific, with orthologous sequences confined to human, chimpanzee, and rhesus macaque.
- Target prediction found 3,527 potential hsa-mir-548 target genes by miRBase/miRanda and 179 Made1-related targets; only 29 genes were shared, close to the random expectation of 27 (P = 0.07), and Made1-related targets were significantly less conserved than miRanda targets (0.082 ± 0.017 vs. 0.319 ± 0.007; t = 11.27, P = 5.7e-29).
- Among 2,045 target genes with Symatlas expression data across 79 tissues, three co-expression clusters (12, 15, and 20) were down-regulated in colorectal adenocarcinoma; the colorectal sample had the lowest average relative expression for target genes (P < 0.001, Tukey test), and 22 putative targets had been previously linked to colorectal cancer by down-regulation.
Methods
- The authors compared hg18 human genome coordinates of experimentally characterized miRNAs from miRBase 8.2 with RepeatMasker-annotated TEs using the UCSC Genome and Table Browsers, then used BLAT, ClustalW, BLASTN against dbEST, Mfold, and UCSC conservation tracks to analyze Made1-derived miRNA sequences.
- Regulatory analysis used miRBase Targets/miRanda predictions plus a search of 3′ UTRs for Made1-derived target sites; random expectation was calculated from joint probabilities and the binomial distribution.
- Expression analysis used Novartis Symatlas profiles across 79 tissues, with Genesis for k-means and hierarchical clustering and GOTree Machine for over-represented Gene Ontology biological process terms.
Limitations
- The paper states that target site predictions are prone to false positives and notes that some up-regulated genes with predicted hsa-mir-548 target sites may be false positives or may reflect translational repression rather than mRNA degradation.
- The paper also notes that the small overlap between miRBase and Made1 target sets may stem from the miRanda conservation criterion and the young evolutionary age of Made1.
- Evident from the text: the MITE-to-miRNA processing model and most regulatory roles are inferred computationally from sequence, expression correlation, and target prediction, without direct experimental validation of processing or repression in this study.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
4 of 39 cited sources checked · 3 supported · 1 flagged · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“TEs also tend to be among the most lineage-specific, i.e. recently evolved, sequences in the human genome [45].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Disputedcites [45] ES Lander, 2001, Initial sequencing and analysis of the human genome., Nature sourceExperimental — accuracy not yet measured
The Transposon-derived repeats section says that most interspersed repeats in the human genome predate the eutherian radiation and that the genome is filled with ancient transposon copies. It identifies some recently active LINE1 subsets, but those exceptions do not support the claim that transposable elements generally tend to be recently evolved, lineage-specific sequences. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Disputed
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
“Consistent with their origin from MITEs, hsa-mir-548 genes are primate-specific and have many potential paralogs in the human genome.”
- Also stated in: § A TE-derived miRNA gene family · hedged
“Each hsa-mir-548 gene showed significant similarity to numerous genomic regions (Table 1), suggesting the possibility that this miRNA gene family may include many as yet uncharacterized members.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § A TE-derived miRNA gene family · hedged
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
“When the log2 median expression ratios were averaged for all genes with putative hsa-mir-548 target sites, the colorectal sample had the lowest relative expression level (q = 9.72, v = 12738, k = 6, P<0.001 Tukey test; Figure 8).”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Each hsa-mir-548 gene showed significant similarity to numerous genomic regions (Table 1), suggesting the possibility that this miRNA gene family may include many as yet uncharacterized members.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > A TE-derived miRNA gene family
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 particular, the mature hsa-mir-548 miRNAs are all 22nt in length, they were identified from a cDNA library made of size fractionated RNA and they map precisely to genomic regions that are predicted to form local hairpin structures.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > A TE-derived miRNA gene family
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“According to the miRBase predictions, the seven hsa-mir-548 genes have 3,527 potential target genes.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“These include a number of genes encoding various immune cell receptors as well as transcription factors and tumor necrosis factors.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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 found 141 human ESTs that showed >80% sequence similarity to the Made1 query sequence over >80% of the length of the element (Table S1).”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > A TE-derived miRNA gene family
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“We found 22 examples of putative hsa-mir-548 target genes that were previously found to be related to colorectal cancer based on down-regulation in six separate microarray studies (Table S4).”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“Three of these clusters – 12, 15 and 20 – showed marked down-regulation of the colorectal adenocarcinoma sample (Figure 6).”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 21
- The quote only partly states this claim. 1
- It may state two separate claims as one. 15
Every source the paper cites for this claim was checked and supports it.
In the paper
“Mature miRNAs are processed from longer RNA sequences that form local stem-loop (hairpin) structures [3].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Introduction
What the sources say
- Supportedcites [3] DP Bartel, 2004, MicroRNAs: genomics, biogenesis, mechanism, and function., Cell source
The supplied passage [3] (labeled Abstract; no page provided) states that miRNAs are processed from transcripts capable of forming local RNA hairpin structures. The biogenesis passage [4] also describes cleavage of a stem-loop precursor to produce the mature miRNA. (LLM, conf=0.95)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“There are two models to explain the repressive effects that miRNAs exert on target gene expression: i-translational repression and ii-mRNA degradation [16], [17], [42].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
What the sources say
- Not checked — no full text of the sourcecites [16] S Yekta, 2004, MicroRNA-directed cleavage of HOXB8 mRNA., Science source
- Not checked yetcites [17] Y Zeng, 2003, MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms., Proc Natl Acad Sci U S A source
Checked before — its earlier verdict is held back until a new check runs.
- Supportedcites [42] T Babak, 2004, Probing microRNAs with microarrays: tissue specificity and functional inference., Rna source
The Conclusions (page not provided) contrast inhibition of translation without target degradation with a mechanism involving tissue-specific mRNA degradation. The paper favors translational inhibition for most mammalian miRNAs, but recognizes both mechanisms described in the claim. (LLM, conf=0.88)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
Every source the paper cites for this claim was checked and supports it.
In the paper
“The connection between TEs and siRNAs has led to the proposal that origination from TEs distinguishes siRNAs from miRNAs [3].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Supportedcites [3] DP Bartel, 2004, MicroRNAs: genomics, biogenesis, mechanism, and function., Cell source
In “Mechanism: Distinctions between miRNAs and siRNAs” (page not provided), the paper identifies origin as a distinction: siRNAs often derive from transposons, whereas miRNAs derive from distinct genomic loci. It presents these differences as a basis for distinguishing the two classes; “often” is an important qualification. (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Supported
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
“This was slightly surprising given that there are 7,850 annotated Made1 sequences in the human genome.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no 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
“There are 29 GO biological process categories, encompassing 104 genes, which contain an over-representation of genes from these clusters (Table S3).”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
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 754 base pair (bp) EST maps to chromosome chr13 at positions 24,718,360–24,719,104; it includes a nearly full length Made1 element as well as 325 bp of 5′ flanking DNA and 353 bp of sequence 3′ to the element.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > A TE-derived miRNA gene family
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“These include genes encoding a cell division cycle protein (ENSG00000004897), a C epsilon type protein kinase (ENSG00000171132) and a centromere/kinetochore protein (ENSG00000086827).”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Visualization of genomic expression data, generated with human genome tilling arrays [30], shows that this particular Made1 is inserted into an intergenic region of the genome that is transcriptionally active (Figure 3).”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > A TE-derived miRNA gene family
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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 intersection of the target gene sets derived from the miRBase versus Made1 consists of a mere 29 genes, and this figure is only slightly higher than the random expectation of 27 shared targets (P = 0.07 binomial distribution).”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“However, as reported here and elsewhere [21], more and more TE-derived miRNAs are being discovered.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked — no full text of the sourcecites [21] NR Smalheiser, 2005, Mammalian microRNAs derived from genomic repeats., Trends Genet source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“TEs, such as Madel, represent a natural source of such lineage-specific miRNAs, which could in turn be responsible for regulatory phenotypes that contribute to evolutionary diversification between species.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“However, a recent report indicated that a number of mammalian miRNAs, including six human miRNAs, are in fact derived from TEs [21].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Introduction
What the sources say
- Not checked — no full text of the sourcecites [21] NR Smalheiser, 2005, Mammalian microRNAs derived from genomic repeats., Trends Genet source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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
“A number of epigenetic gene silencing mechanisms, such as cytosine methylation [52], genomic imprinting [53] and heterochromatin [54] are thought to have evolved as defense mechanisms against transposition.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked — no full text of the sourcecites [52] JA Yoder, 1997, Cytosine methylation and the ecology of intragenomic parasites., Trends Genet source
- Not checked — no full text of the sourcecites [53] JF McDonald, 2005, Host defenses to transposable elements and the evolution of genomic imprinting., Cytogenet Genome Res source
- Not checked — no full text of the sourcecites [54] Z Lippman, 2004, Role of transposable elements in heterochromatin and epigenetic control., Nature source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“A striking feature of plant MITEs is their apparent preference for insertion in gene regions [49], [50].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked yetcites [49] L Mao, 2000, Rice transposable elements: a survey of 73,000 sequence-tagged-connectors., Genome Res source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked yetcites [50] Q Zhang, 2000, Recent, extensive, and preferential insertion of members of the miniature inverted-repeat transposable element family Heartbreaker into genic regions of maize., Proc Natl Acad Sci U S A source
Checked before — its earlier verdict is held back until a new check runs.
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“This would provide ample opportunities for the processing of MITE hairpins by RNA interference enzymatic machinery, which is known to play a particularly important role in plant gene regulation [51].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked yetcites [51] MA Matzke, 2004, Planting the seeds of a new paradigm., PLoS Biol source
Checked before — its earlier verdict is held back until a new check runs.
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not checked yet
In the paper
“Hsmar1 elements are DNA-type TEs, approximately 1,300 bp in length, which possess a transposase-encoding open reading frame flanked by terminal inverted repeat (TIR) sequences (Figure 2A) [41].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > A TE-derived miRNA gene family
What the sources say
- Not checked — no full text of the sourcecites [41] HM Robertson, 1997, Molecular evolution of an ancient mariner transposon, Hsmar1, in the human genome., Gene source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Muk is an effective silencer of the MuDR DNA-type TE, and the Muk locus consists of an inverted duplication of a partially deleted MuDR element.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked — no full text of the sourcecites [19] RK Slotkin, 2005, Heritable transposon silencing initiated by a naturally occurring transposon inverted duplication., Nat Genet source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“In addition, the dispersed repetitive nature of TE sequences provides for the emergence of multiple novel miRNA genes as well as numerous homologous target sites throughout the genome.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“The evolutionary lineage-specific nature of MITEs could also provide for the generation of novel regulatory phenotypes related to species diversification.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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
“Therefore, we propose a model whereby Made1 insertions into transcriptionally active genomic regions would yield viable pri-miRNA structures that would be processed into mature miRNA sequences by the RNA interference enzymatic machinery.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > A TE-derived miRNA gene family
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Made1 insertions generally occur in transcriptionally active genomic regions.
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
“Apparently, Made1 sequences avoid protein coding gene exon regions and thus are poorly represented among potential hsa-mir-548 target sites.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Consistent with this model, there are a number of cases of siRNAs that originate from TEs in different species [55]–[58].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked yetcites [55] AA Aravin, 2003, The small RNA profile during Drosophila melanogaster development., Dev Cell source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked yetcites [56] A Hamilton, 2002, Two classes of short interfering RNA in RNA silencing., Embo J source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked yetcites [57] Z Lippman, 2003, Distinct mechanisms determine transposon inheritance and methylation via small interfering RNA and histone modification., PLoS Biol source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked — no full text of the sourcecites [58] D Zilberman, 2003, ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation., Science source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Not checked yet
In the paper
“MITEs are widely distributed among eukaryotes [46]”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked — no full text of the sourcecites [46] C Feschotte, 2002, Miniature inverted-repeat transposable elements and their relationship to established DNA transposons. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“When Muk is transcribed, it yields a long (>2 kb) dsRNA hairpin structure that is processed to yield siRNAs.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked — no full text of the sourcecites [19] RK Slotkin, 2005, Heritable transposon silencing initiated by a naturally occurring transposon inverted duplication., Nat Genet source
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“For instance, MITEs are particularly prevalent in plants where they were first discovered [47]”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked — no full text of the sourcecites [47] TE Bureau, 1992, Tourist: a large family of small inverted repeat elements frequently associated with maize genes., Plant Cell source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Including these new data, version 8.2 of miRBase, the online microRNA database [11], reports 462 human miRNA genes.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Introduction
What the sources say
- Not checked yetcites [11] S Griffiths-Jones, 2006, miRBase: microRNA sequences, targets and gene nomenclature., Nucleic Acids Res source
Checked before — its earlier verdict is held back until a new check runs.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Not checked yet
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
“The tight hairpin formed by the element is similar to the structures processed by Drosha and Dicer, and the location of the mature miRNA sequence, in the stem close to the 3′ end of the structure, is consistent with the mode of cleavage thought to be employed by the Dicer (Figure 4B).”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > A TE-derived miRNA gene family
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“In a similar way, RNA interference by siRNAs is considered to have evolved to silence TEs [18], [20].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked — no full text of the sourcecites [18] MA Matzke, 2000, Transgene silencing by the host genome defense: implications for the evolution of epigenetic control mechanisms in plants and vertebrates., Plant Mol Biol source
- Not checked — no full text of the sourcecites [20] NL Vastenhouw, 2004, RNAi protects the Caenorhabditis elegans germline against transposition., Trends Genet source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“the rice genome alone contains ∼90,000 MITEs [48].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked — no full text of the sourcecites [48] N Jiang, 2004, Using rice to understand the origin and amplification of miniature inverted repeat transposable elements (MITEs)., Curr Opin Plant Biol source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“a recent analysis of the human genome detected numerous putative miRNAs that are not evolutionarily conserved [5].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked — no full text of the sourcecites [5] I Bentwich, 2005, Identification of hundreds of conserved and nonconserved human microRNAs., Nat Genet source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Recently, anti-correlated expression patterns between miRNA sequences and their target mRNAs have provided evidence in favor of the mRNA degradation model [43].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Regulatory effects of hsa-mir-548
What the sources say
- Not matchedcites [43] JC Huang, 2006, Detecting microRNA targets by linking sequence, microRNA and gene expression data.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- 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
“Such panhandle structures would include long internal loop regions that correspond to the internal open reading frames that are lost when autonomous elements are converted to non-autonomous MITE derivatives.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Many of the extant miRNA genes characterized today may have evolved beyond recognition to their progenitor TEs, while others may have originated from other genomic re-structuring mechanisms that juxtapose short inverted repeats [59].”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
What the sources say
- Not checked — no full text of the sourcecites [59] E Allen, 2004, Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana., Nat Genet source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“MITEs retain the TIRs, and those same TIRs that were processed from longer RNAs to form siRNA could be similarly processed to form miRNAs.”
§ A Family of Human MicroRNA Genes from Miniature Inverted-Repeat Transposable Elements > Results and Discussion > Conclusion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Made1 is an evolutionarily young TE family.
“the fact that Made1 is an evolutionarily young TE family.”
The paper relies on this without support.
The putative hsa-mir-548 target genes identified by miRBase predictions are actual regulatory targets of hsa-mir-548.
“There are more than 3,500 putative hsa-mir-548 target genes; analysis of their expression profiles and functional affinities suggests cancer-related regulatory roles for hsa-mir-548.”
The paper relies on this without support.
Made1 insertions generally occur in transcriptionally active genomic regions.
“Made1 insertions into transcriptionally active genomic regions would yield viable pri-miRNA structures that would be processed into mature miRNA sequences by the RNA interference enzymatic machinery.”
The paper relies on this without support.
Target site predictions are prone to false positives.
“Consideration of target gene relative expression levels can also be used to help validate target site predictions, which are prone to false positives.”
The paper relies on this without support.
The tissue samples used for expression analysis are similar to the colorectal samples from which hsa-mir-548 genes were cloned.
“We sought to further evaluate the potential mRNA degradation-based regulatory effects of the hsa-mir-548 miRNAs by searching for down regulation of putative target genes in tissue samples similar to the colorectal samples from which they were cloned [10].”
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Metadata
- Authors
- Piriyapongsa, J., & Jordan, I. K.
- Affiliations
- Georgia Institute of Technology (US)
- Corresponding author
- Jordan, I. King
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-02-14
- Volume
- 2
- Issue
- 2
- Pages
- e203
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC1784062
- OpenAlex
- W2074216902
- Cited by
- 283
- References
- 68
- Citations by year
- 2026: 2 · 2025: 4 · 2023: 5 · 2022: 13 · 2021: 13 · 2020: 12 · 2019: 12 · 2018: 13 · 2017: 11 · 2016: 15 · 2015: 23 · 2014: 14 · 2013: 25 · 2012: 28
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- SMARTech Repository (Georgia Institute of Technology) (submittedVersion, cc-by)
- Funders
- Georgia Institute of Technology
- Ministry of Science and Technology of Thailand
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- microRNA, miniature inverted-repeat transposable elements, RNA interference, small regulatory RNAs, paralogs, target genes, genome evolution
- MeSH terms
- Animals, Base Sequence, DNA Transposable Elements, Multigene Family, Humans, Mammals, Molecular Sequence Data, Sequence Homology, Nucleic Acid, Sequence Alignment, Expressed Sequence Tags, RNA Interference, RNA, Small Interfering, MicroRNAs, Comparative Genomic Hybridization, Inverted Repeat Sequences
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 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (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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