MicroRNA expression in the adult mouse central nervous system

In the paper

“while computational predictions estimate that the vertebrate genomes may contain up to z1000 miRNA genes (Bentwich et al. 2005;Berezikov et al. 2005).”

What the sources say

• ?Not checked — no full text of the sourcecites Bentwich et al. 2005 source
• Supported

  The paper’s Abstract says it may be possible that as many as 1,000 miRNAs exist in a vertebrate genome. This matches the citing sentence’s hedged estimate, which the paper relates to candidates missed by its computational comparisons. (LLM, conf=0.94)

  cites Berezikov et al. 2005 source

In the paper

“Animal miRNAs have emerged as important players in the control of diverse biological processes (Bartel 2004;Wienholds and Plasterk 2005;Kloosterman and Plasterk 2006).”

What the sources say

• Supported

  In “Function: Roles of Animal miRNAs” (indexed under Abstract; page unavailable), the review says predicted mammalian miRNA targets span a broad diversity of biological processes and that miRNAs appear to regulate a diverse set of genes at many levels. This supports the citing sentence’s broad characterization of animal miRNAs as important regulators. (LLM, conf=0.88)

  cites Bartel 2004 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Wienholds and Plasterk 2005
• Supported

  The Abstract says miRNAs control gene expression and implicates them in tissue morphogenesis, apoptosis, signaling pathways, and disease. The Concluding Remarks likewise describe their importance in animal development and disease-related processes, supporting the broad claim. (LLM, conf=0.94)

  cites Kloosterman and Plasterk 2006 source

In the paper

“miRNAs are generated from long primary transcripts that are processed in multiple steps to cytoplasmic z22 nucleotide (nt) mature miRNAs (Bartel 2004;Du and Zamore 2005;Zeng 2006).”

What the sources say

• Supported

  The biogenesis discussion (indexed as Abstract; page unavailable) describes long pri-miRNAs, export of their precursors to the cytoplasm, and sequential processing by Drosha and Dicer. It also describes miRNAs processed from precursor stem loops as approximately 22 nt long. (LLM, conf=0.90)

  cites Bartel 2004 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Du and Zamore 2005
• ?Not checked — no full text of the sourcecites Zeng 2006 source

In the paper

“During development, many miRNAs are expressed in neurons or show distinct expression patterns within the developing central nervous system (CNS), implying their importance in brain development and function (Krichevsky et al. 2003;Miska et al. 2004;Sempere et al. 2004;Smirnova et al. 2005;Wienholds et al. 2005).”

What the sources say

• Supported

  The Introduction describes miRNAs isolated from embryonic neurons and brain, including some that are neuron-specific. In “miRNA expression during corticogenesis,” the paper reports distinct changes in miRNA expression across stages of rat forebrain development; the Introduction frames these findings as relevant to brain development. Page numbers are not provided in our copy. (LLM, conf=0.89)

  cites Krichevsky et al. 2003 source
• Partly supported

  The Results and discussion section reports distinct temporal miRNA expression patterns in whole mouse brains, and the Conclusions speculate that some developmentally regulated miRNAs play roles in brain development. Because the samples were whole brains, the paper does not establish expression specifically in neurons or distinct patterns across CNS regions; it also does not establish a role in brain function. (LLM, conf=0.82)

  cites Miska et al. 2004 sourceExperimental — accuracy not yet measured
• Supported

  The Results and discussion section reports that 19 miRNAs were induced during differentiation of mouse and human cells into neurons. The Conclusions say these findings strongly suggest a role for brain-expressed miRNAs in neuronal development, supporting the neuronal-expression branch of the citing sentence. (LLM, conf=0.88)

  cites Sempere et al. 2004 source

In the paper

“microRNAs are ;22 nucleotide endogenous noncoding RNAs that post-transcriptionally repress expression of protein-coding genes by base-pairing with the 39-untranslated regions of the target mRNAs.”

• Also stated in: § INTRODUCTION · plain

  “MicroRNAs (miRNAs) are small, endogenous noncoding RNA molecules that post-transcriptionally regulate expression of protein-coding genes (Bartel 2004;Kloosterman and Plasterk 2006).”

What the sources say

• Partly supported

  The Abstract describes miRNAs as endogenous ~22-nucleotide RNAs that regulate mRNAs through cleavage or translational repression, and the Main Text gives an example of pairing with a target’s 3′ UTR. But the paper cautions that it is premature to conclude that most metazoan miRNA regulation occurs through 3′-UTR sites, so the claim presents that location too generally. (LLM, conf=0.88)

  cites Bartel 2004 sourceExperimental — accuracy not yet measured
• Partly supported

  The Abstract says miRNAs control gene expression through translational inhibition and mRNA destabilization, and a passage labeled Abstract describes miRNA target sites in 3′UTRs that can produce strong repression. The retrieved passages do not establish the claimed approximately 22-nucleotide length or explicitly describe miRNAs as endogenous noncoding RNAs. (LLM, conf=0.82)

  cites Kloosterman and Plasterk 2006 sourceExperimental — accuracy not yet measured

In the paper

“Regional coexpression of miRNAs and their targets has been reported.”

What the sources say

• ?Not checked — no full text of the sourcecites Abelson et al. 2005 source
• Supported

  The Results and Discussion section reports that miR-200b expression overlaps with that of its target Zfhx1b in several regions of the adult mouse brain, including the hippocampus and cerebellum. The paper explicitly calls this regional coexpression; no page number is provided in the copy. (LLM, conf=0.94)

  cites Christoffersen et al. 2007 source

In the paper

“other miRNAs are temporally expressed during development of the CNS being repressed in the mature CNS (Miska et al. 2004).”

What the sources say

• Partly supported

  The Results and discussion section (page unavailable) reports that many miRNAs peak during fetal, neonatal, or juvenile mouse brain development, with lower expression at other stages. It does not establish that these miRNAs are actively repressed in maturity, and its measurements are from brain rather than the entire CNS. (LLM, conf=0.83)

  cites Miska et al. 2004 sourceExperimental — accuracy not yet measured

In the paper

“while another study has reported altered miRNA profiles in the prefrontal cortex of patients with schizophrenia and schizoaffective disorder (Perkins et al. 2007).”

What the sources say

• Supported

  The Results section reports 16 differentially expressed miRNAs in prefrontal cortex tissue from subjects with schizophrenia (n = 13) or schizoaffective disorder (n = 2), compared with 21 psychiatrically unaffected individuals. This directly supports the citing sentence’s report of altered miRNA profiles in those groups. (LLM, conf=0.94)

  cites Perkins et al. 2007 source

In the paper

“While miR-124a expression can be detected in E11.5 mouse embryos and it continues to be expressed in neurons of adult mice (Miska et al. 2004;Visvanathan et al. 2007)”

What the sources say

• Partly supported

  The Results and discussion section reports miR-124a in brain and studies mouse brain samples from E12.5 through adulthood; the Northern blots methods also list a miR-124a probe. The paper does not examine E11.5 embryos or establish that expression in adult mice is specifically in neurons rather than whole brain. (LLM, conf=0.84)

  cites Miska et al. 2004 sourceExperimental — accuracy not yet measured
• Partly supported

  The section on SCP1 and P19 cells says miR-124 expression is maintained throughout adulthood and discusses possible roles in mature neurons. The copy does not establish detection specifically in E11.5 mouse embryos or explicitly locate the adult expression in mouse neurons; the embryonic neural-tube experiments described here used chicks (Fig. 3). (LLM, conf=0.86)

  cites Visvanathan et al. 2007 sourceExperimental — accuracy not yet measured

In the paper

“In addition, conditional ablation of Dicer in murine post-mitotic Purkinje cells resulted in progressive loss of miRNAs, cerebellar degeneration, and development of ataxia (Schaefer et al. 2007).”

What the sources say

• Supported

  The Results and Discussion section describes conditional, postnatal Dicer ablation in mouse Purkinje cells after they had become postmitotic. Its sections on miRNA expression, degeneration, and ataxia report declining miRNA levels, subsequent Purkinje cell and cerebellar degeneration, and the development of ataxia. (LLM, conf=0.94)

  cites Schaefer et al. 2007 source

In the paper

“Background-subtracted spot intensities were normalized using variance stabilization normalization (Huber et al. 2002).”

What the sources say

• Supported

  The Introduction identifies the paper’s method as a model-based approach to normalization, and The Model describes applying a variance-stabilizing transformation to spot intensities. The Validation section discusses intensities after subtraction of the image-analysis background estimates, so the citation supports using this method for background-subtracted spot intensities. (LLM, conf=0.90)

  cites Huber et al. 2002 source

In the paper

“For example, miR-1 is highly prevalent in the heart and skeletal muscle, whereas the predicted targets of miR-1 are expressed at significantly lower levels in heart and skeletal muscle compared to other tissues (Sood et al. 2006).”

What the sources say

• Supported

  The Results identify miR-1 as highly specifically expressed in heart and skeletal muscle. The gene-centric analysis reports that its predicted targets are expressed at significantly lower levels there than in other tissues; Table 1 ranks those tissues first and second for this finding. Page numbers are not provided in our copy. (LLM, conf=0.94)

  cites Sood et al. 2006 source

In the paper

“Many miRNAs located within protein-coding and nonprotein-coding genes are transcriptionally linked to the expression of their host genes (Rodriguez et al. 2004).”

What the sources say

• Partly supported

  The Conclusion says a large subset of mammalian miRNAs may be transcriptionally linked to the expression of protein-coding and noncoding host genes. The citing sentence captures the populations and relationship but states the linkage as fact, whereas the paper presents it as a possibility supported by its findings. (LLM, conf=0.85)

  cites Rodriguez et al. 2004 sourceExperimental — accuracy not yet measured

In the paper

“In the developing chick neural tube, miR-124a is a component of a regulatory network, which controls the transition between neural progenitors and post-mitotic neurons, by suppressing the anti-neural factor SCP1 (Visvanathan et al. 2007).”

What the sources say

• Supported

  In “miR-124 stimulates neuronal differentiation in the developing spinal cord” (page not provided), the paper reports chick neural-tube experiments and concludes that SCP1 is a key miR-124 target during the conversion of progenitors to neurons. In “SCP1 antagonizes miR-124-mediated neurogenesis of P19 cells” (page not provided), it proposes a REST/SCP1–miR-124 regulatory feedback loop governing that transition. (LLM, conf=0.93)

  cites Visvanathan et al. 2007 source

In the paper

“Significance analysis of microarrays (SAM) was used to identify miRNAs differentially expressed between samples (FDR = 0) (Tusher et al. 2001).”

What the sources say

• Supported

  The Abstract identifies Tusher et al. as the developers of SAM, a method for detecting differential expression and estimating the false discovery rate. The citation supports the identification of the method; the miRNA analysis and FDR = 0 describe the citing authors’ application, not a result attributed to Tusher et al. (LLM, conf=0.88)

  cites Tusher et al. 2001 source

In the paper

“On the other hand, expression profiling in adult tissues has identified miRNAs enriched in the CNS, suggesting that these miRNAs could play important regulatory roles in mature neurons (Babak et al. 2004;Barad et al. 2004;Miska et al. 2004;Sempere et al. 2004;Thomson et al. 2004).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Babak et al. 2004
• Partly supported

  The Results and Discussion report expression profiling of human tissues and identify brain-specific miRNAs, including MIR-9 and MIR-124A. The paper does not establish that the samples were adult tissues or that these miRNAs have regulatory roles in mature neurons; its profiling used whole-brain RNA rather than isolated neurons. Page numbers were not available in our copy. (LLM, conf=0.84)

  cites Barad et al. 2004 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and discussion section reports expression profiling of whole mouse brains, including 4-month-old adults, and identifies twelve microRNAs with their highest signals at the adult stage. It does not compare adult brain with other tissues to establish CNS enrichment, and its proposed regulatory roles concern brain development rather than mature neurons. (LLM, conf=0.86)

  cites Miska et al. 2004 sourceExperimental — accuracy not yet measured

In the paper

“Consistent with our array results, we observed strong in situ signals for miR-200b in coronal sections of the olfactory bulb (Fig. 3I, inset), whereas weaker signals were observed in other regions of the brain (Fig. 3I).”

In the paper

“This is consistent with miR-10a being located within Hoxd4 (ENSMUST00000047904), which also shows highest expression levels in the spinal cord and medulla oblongata.”

In the paper

“miR-375, miR-141, and miR-200a in the pituitary (Landgraf et al. 2007);”

What the sources say

• ?Not checked — no full text of the sourcecites Landgraf et al. 2007 source

In the paper

“Examples of miRNAs with conserved expression include miR-200b and miR-375 and miR-204, which are enriched in the olfactory bulb, pituitary, and eye, respectively, as well as miR-96, which is enriched in the olfactory bulb and eye.”

In the paper

“Furthermore, miR-96, miR-200a, miR-200b, miR-141, and miR-183 all are predicted to be expressed in the olfactory epithelium, which is consistent with our results showing enrichment of these miRNAs in the olfactory bulb.”

In the paper

“However, we could not confirm pituitaryspecific enrichment of miR-25, as it was also found to be enriched in medulla oblongata, spinal cord, pons, and mesencephalon by real-time RT-PCR (Fig. 3G).”

In the paper

“Clear examples of divergent expression patterns between zebrafish and mouse CNS are miR-31, which is enriched in the eye in mice, whereas it is ubiquitously expressed in zebrafish;”

In the paper

“whereas in situ detection of miR-218 showed weak expression in most regions (Fig. 3K), concurring with our miRNA array data.”

In the paper

“Additionally, miR-142-3p expression is enriched in the medulla oblongata and spinal cord in mice but confined to the thymus and blood cells in zebrafish.”

In the paper

“For example, miR-375 and miR-7 are predicted to be expressed in the pituitary and, indeed, our results show highest accumulation of both miR-7 and miR-375 in the pituitary.”

What the sources say

• ?Not checked — no full text of the sourcecites Farh et al. 2005 source

In the paper

“In contrast, the expression patterns of 21 mouse CNS-enriched miRNAs appeared to be divergent from those of zebrafish, although the mature miRNA sequences are nearly 100% conserved between the two vertebrates, while all except four miRNAs show 100% conservation in their seed regions (Table 1).”

In the paper

“Another example is the pituitary-specific miR-152, which at the genomic level is localized within the Copz2 gene, which also shows most prevalent expression in the pituitary.”

In the paper

“and miR-195, which in mice is enriched in the cerebellum, whereas in zebrafish it displays widespread expression.”

In the paper

“and that miR-204 and miR-205 are prevalently expressed in the eye”

In the paper

“Most animal miRNAs recognize their target sites located in 39 UTRs by incomplete basepairing, resulting in mRNA destabilization or translational repression of the target genes (He and Hannon 2004;Bushati and Cohen 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites He and Hannon 2004 source
• ?Not checked — no full text of the sourcecites Bushati and Cohen 2007 source

In the paper

“To date, 442 murine miRNA sequences have been deposited in the miRBase (Griffiths-Jones et al. 2006)”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Griffiths-Jones et al. 2006

In the paper

“Error bars of real-time RT-PCR data indicate the standard error of the mean of three biological replicates; error bars of microarray data indicate the standard error of the mean of three replica hybridizations.”

In the paper

“For example, a mutation in the target site of miR-189 in the human SLITRK1 gene has been shown to be associated with Tourette's syndrome (Abelson et al. 2005)”

What the sources say

• ?Not checked — no full text of the sourcecites Abelson et al. 2005 source

In the paper

“Shown are the average ratios of three replica hybridizations.”

In the paper

“Brainarea-enriched miRNAs were identified by one-sample t-tests using pooled variances (P < 0.05).”

In the paper

“While plant miRNAs are generally perfectly complementary to their target mRNAs, most animal miRNAs pair to the 39 UTRs of their targets by incomplete base-pairing, in which nucleotides 2-7 of the mature miRNA sequence, termed the seed region, appear to be critical for target site recognition (Lewis et al. 2005).”

What the sources say

• ?Not checked — no full text of the sourcecites Lewis et al. 2005 source

In the paper

“Additionally, luciferase reporter assays have identi-fied myotrophin (Mtpn) as a target of miR-124 regulation (Krek et al. 2005), both of which are highly expressed in neurons throughout the brain (Fujigasaki et al. 1996).”

What the sources say

• ?Not checked — no full text of the sourcecites Krek et al. 2005 source
• ?Not checked — no full text of the sourcecites Fujigasaki et al. 1996 source

In the paper

“This is supported by a study, which showed that miR-134, a brainspecific microRNA, is present in dendrites, where it represses the local synthesis of the protein kinase Limk1 to regulate spine size (Schratt et al. 2006).”

What the sources say

• ?Not checked — no full text of the sourcecites Schratt et al. 2006 source

In the paper

“Recent reports suggest that miRNAs can regulate dendritic spine size (Schratt et al. 2006) and neuronal morphogenesis (Vo et al. 2005), whereas massive parallel sequencing of small RNA libraries from human and chimpanzee brain has revealed highly complex miRNA repertoires in the primate brain (Berezikov et al. 2006).”

What the sources say

• ?Not checked — no full text of the sourcecites Schratt et al. 2006 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Vo et al. 2005
• ?Not checked — no full text of the sourcecites Berezikov et al. 2006 source

In the paper

“For example, while miR-125b is ubiquitously expressed in the brain and spinal cord of zebrafish, its expression is confined to the mid-hindbrain boundary in the mouse (Ason et al. 2006).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ason et al. 2006

In the paper

“In conclusion, the inventory of miRNA profiles in the adult mouse CNS presented here provides an important step toward further elucidation of miRNA function and miRNA-related gene regulatory networks in the mammalian central nervous system.”

In the paper

“suggest that these miRNAs might be coexpressed with their targets.”

In the paper

“Relative expression was calculated using the DDC T method (Livak and Schmittgen 2001) and normalized to the expression of snoRNA202 (Applied Biosystems).”

What the sources say

• ?Not checked — no full text of the sourcecites Livak and Schmittgen 2001 source

In the paper

“Maternal-zygotic dicer mutant zebrafish that lack all mature miRNAs display abnormal brain morphogenesis and neural differentiation (Giraldez et al. 2005).”

What the sources say

• ?Not checked — no full text of the sourcecites Giraldez et al. 2005 source

In the paper

“Interestingly, many neuronal miRNAs appear to be localized to actively translating polyribosomes in dendrites, where they may control localized translation of dendrite-specific mRNAs (Kim et al. 2004).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Kim et al. 2004

In the paper

“Stimulation of neurons relieves miR-134-mediated inhibition of Limk1 translation, which, in turn, may contribute to synaptic plasticity (Schratt et al. 2006).”

What the sources say

• ?Not checked — no full text of the sourcecites Schratt et al. 2006 source

In the paper

“Notably, injection of miR-430 rescues the brain defects in the mutant embryos, inferring a general role in zebrafish brain morphogenesis.”

What the sources say

• ?Not checked — no full text of the sourcecites Giraldez et al. 2005 source

In the paper

“Highly divergent expression patterns of conserved miRNAs in zebrafish, medaka, chicken, and mouse have previously been reported (Ason et al. 2006).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ason et al. 2006

In the paper

“P-values were adjusted for multiple comparisons using the Bonferroni procedure.”

• Also stated in: § Detection of spatial miRNA accumulation by in situ hybridization · plain

  “P-values were adjusted for multiple comparisons using the Bonferroni procedure.”