CoChat
Sign Up
Cited by 463MicroRNA in disease regulationPlant Molecular Biology ResearchDevelopmental Biology and Gene Regulation

MicroRNA expression in the adult mouse central nervous system

Open access
Bak, Mads, Silahtaroglu, Asli, Møller, Morten, Christensen, Mette, Rath, Martin F., Skryabin, Boris, Tommerup, Niels, Kauppinen, Sakari·2008·RNA
DOI 10.1261/rna.783108PMC PMC2248253
Open this paper in CoChat — free accountOpen PDF

Abstract

microRNAs are ∼22 nucleotide endogenous noncoding RNAs that post-transcriptionally repress expression of protein-coding genes by base-pairing with the 3′-untranslated regions of the target mRNAs. We present here an inventory of miRNA expression profiles from 13 neuroanatomically distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons, hypothalamus, hippocampus, neocortex, olfactory bulb, eye, and pituitary gland. These findings suggest that a large number of mouse CNS-expressed miRNAs may be associated with specific functions within these regions. Notably, more than 50% of the identified mouse CNS-enriched miRNAs showed different expression patterns compared to those reported in zebrafish, although the mature miRNA sequences are nearly 100% conserved between the two vertebrate species. 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.

AI snapshot

Written from the paper’s full text.

TL;DR

This study inventories miRNA expression across 13 adult mouse CNS regions using LNA microarrays, RT-PCR, and LNA-ISH, identifying 44 miRNAs with more than threefold regional enrichment. It reports substantial divergence from zebrafish expression patterns despite high sequence conservation, providing region-specific miRNA candidates for CNS function.

Key findings

  • Microarray profiling of 13 neuroanatomically distinct adult mouse CNS areas found 63 miRNAs differentially expressed within the CNS by SAM (FDR = 0), and 44 miRNAs with more than threefold enrichment in specific regions; no enrichment was detected in amygdala, mesencephalon, or thalamus.
  • Region-enriched examples included miR-195, miR-497, and miR-30b in cerebellum; miR-34a, miR-451, miR-219, miR-338, miR-10a, and miR-10b in medulla oblongata; miR-7 and miR-7b in hypothalamus; and miR-218, miR-221, miR-222, miR-26a, miR-128a/b, miR-138, and let-7c in hippocampus.
  • Validation by real-time RT-PCR showed strong correlation with microarray data (R² = 0.63; R² = 0.93 after removing two outliers); miR-34a was approximately sixfold to ninefold higher in spinal cord, medulla oblongata, and pons compared with whole mouse brain.
  • Comparison with zebrafish found conserved expression for 15 of 36 miRNAs, while 21 mouse CNS-enriched miRNAs showed divergent expression patterns despite nearly 100% mature miRNA sequence conservation and all except four miRNAs showing 100% seed-region conservation.

Methods

  • Dissected 13 CNS regions from three adult male Balb/c mice, pooled total RNA, and hybridized to spotted LNA-modified miRNA microarrays covering all mouse miRNAs in miRBase release 7.1; whole brain RNA from two mice was also analyzed individually.
  • Differential expression used SAM (FDR = 0), followed by one-sample t-tests with pooled variances (P < 0.05) and Bonferroni adjustment; region-enriched miRNAs were defined as more than threefold above average expression across all 13 regions.
  • Real-time RT-PCR used TaqMan MicroRNA Assays with ΔΔCT normalization to snoRNA202; LNA-based in situ hybridization was performed on 10-µm cryosections of adult mouse brain with DIG-labeled probes and tyramide signal amplification.

Limitations

  • The paper states that failure to identify coexpression of a miRNA and its host gene does not exclude shared transcriptional control elements, and that differences in turnover or processing could produce different expression levels within the same tissue.
  • The paper reports that pituitary-specific enrichment of miR-25 could not be confirmed by real-time RT-PCR, as it was also enriched in medulla oblongata, spinal cord, pons, and mesencephalon.
  • Evident from the text: spatial validation by LNA-ISH was limited to selected miRNAs (miR-128, miR-200b, miR-195, and miR-218), and the study does not include functional perturbation or direct target validation in the mouse CNS.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1261/rna.783108

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 61 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    miR-34a expression was approximately sixfold to ninefold higher in the spinal cord, medulla oblongata, and pons compared to whole mouse brain.

    “Expression of miR-34a was approximately sixfold to ninefold higher in the spinal cord, medulla oblongata, and pons compared to whole mouse brain;”
    Quote in the paperNot a substantial claim
  • Findingown data

    The hippocampus showed accumulation of miR-218, miR-221, miR-222, miR-26a, miR-128a/b, miR-138, and let-7c.

    “The hippocampus showed accumulation of miR-218, miR-221, miR-222, miR-26a, miR-128a/b, miR-138, and let-7c.”
    Quote in the paperSubstantial claim
  • Findingown data

    The strongest in situ hybridization signal for miR-195 was detected in the cerebellum.

    “The strongest in situ hybridization signal for miR-195 was detected in the cerebellum (Fig. 3J)”
    • Also stated in: § Detection of spatial miRNA accumulation by in situ hybridization · plain
      “(J) The strongest in situ hybridization signal for miR-195 was detected in the cerebellum, whereas (K) in situ detection of miR-218 showed weak expression in most regions.”
    Quote in the paperNot a substantial claim
  • Findingcitation

    miR-195 was enriched in the cerebellum.

    “miR-195 in the cerebellum (Hohjoh and Fukushima 2007);”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hohjoh and Fukushima 2007

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

  • Findingown data

    Many of the highly enriched miRNAs appeared to be widely expressed in the central nervous system.

    “Many of these miRNAs appeared to be widely expressed in the central nervous system.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 28
  • Classified as probably not a substantial claim. 31

  • May combine two claims.

    Findingown data

    Strong in situ signals for miR-200b were observed in coronal sections of the olfactory bulb, whereas weaker signals were observed in other regions of the brain.

    “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).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    miR-10a is located within Hoxd4, which shows highest expression levels in the spinal cord and medulla oblongata.

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

  • May combine two claims.

    Findingcitation

    miR-375, miR-141, and miR-200a were enriched in the pituitary.

    “miR-375, miR-141, and miR-200a in the pituitary (Landgraf et al. 2007);”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Landgraf et al. 2007 source

  • May combine two claims.

    Findingown data

    miR-200b, miR-375, and miR-204 are enriched in the olfactory bulb, pituitary, and eye, respectively, and miR-96 is enriched in the olfactory bulb and eye.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    miR-96, miR-200a, miR-200b, miR-141, and miR-183 are predicted to be expressed in the olfactory epithelium, consistent with the authors' results showing enrichment of these miRNAs in the olfactory bulb.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Pituitary-specific enrichment of miR-25 could not be confirmed; it was also found to be enriched in medulla oblongata, spinal cord, pons, and mesencephalon by real-time RT-PCR.

    “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).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    miR-31 is enriched in the eye in mice, whereas it is ubiquitously expressed in zebrafish.

    “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;”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In situ detection of miR-218 showed weak expression in most regions, concurring with miRNA array data.

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

  • May combine two claims.

    Findingnone given

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    miR-375 and miR-7 are predicted to be expressed in the pituitary, and the authors' results show highest accumulation of both miR-7 and miR-375 in the pituitary.

    “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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Farh et al. 2005 source

  • May combine two claims.

    Findingown data

    The expression patterns of 21 mouse CNS-enriched miRNAs appeared divergent from those of zebrafish, although mature miRNA sequences are nearly 100% conserved between the two vertebrates, while all except four miRNAs show 100% conservation in their seed regions.

    “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).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    miR-152 is localized within the Copz2 gene, which shows most prevalent expression in the pituitary.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

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

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

  • May combine two claims.

    Findingown data

    miR-204 and miR-205 are prevalently expressed in the eye.

    “and that miR-204 and miR-205 are prevalently expressed in the eye”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Computational predictions estimate that vertebrate genomes may contain up to ~1000 miRNA genes.

    “while computational predictions estimate that the vertebrate genomes may contain up to z1000 miRNA genes (Bentwich et al. 2005;Berezikov et al. 2005).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Bentwich et al. 2005 source
    • cites Berezikov et al. 2005 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Most animal miRNAs recognize target sites in 3' UTRs by incomplete base-pairing, resulting in mRNA destabilization or translational repression of target genes.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites He and Hannon 2004 source
    • cites Bushati and Cohen 2007 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Animal miRNAs are important players in the control of diverse biological processes.

    “Animal miRNAs have emerged as important players in the control of diverse biological processes (Bartel 2004;Wienholds and Plasterk 2005;Kloosterman and Plasterk 2006).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bartel 2004 source
    • cites Wienholds and Plasterk 2005

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

    • cites Kloosterman and Plasterk 2006 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    miRNAs are generated from long primary transcripts that are processed in multiple steps to cytoplasmic ~22 nucleotide mature miRNAs.

    “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).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bartel 2004 source
    • cites Du and Zamore 2005

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

    • cites Zeng 2006 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    During development, many miRNAs are expressed in neurons or show distinct expression patterns within the developing CNS, implying their importance in brain development and function.

    “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).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Krichevsky et al. 2003 source

      Queued — the background check reaches it, usually within a day.

    • cites Miska et al. 2004 source
    • cites Sempere et al. 2004 source

      Queued — the background check reaches it, usually within a day.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    microRNAs are ~22 nucleotide endogenous noncoding RNAs that post-transcriptionally repress expression of protein-coding genes by base-pairing with the 3' untranslated regions of target mRNAs.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Bartel 2004 source
    • cites Kloosterman and Plasterk 2006 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    442 murine miRNA sequences have been deposited in miRBase.

    “To date, 442 murine miRNA sequences have been deposited in the miRBase (Griffiths-Jones et al. 2006)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Griffiths-Jones et al. 2006

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

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A mutation in the target site of miR-189 in the human SLITRK1 gene is associated with Tourette's syndrome.

    “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)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Abelson et al. 2005 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Regional coexpression of miRNAs and their targets has been reported.

    “Regional coexpression of miRNAs and their targets has been reported.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Abelson et al. 2005 source
    • cites Christoffersen et al. 2007 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The shown data are average ratios of three replica hybridizations.

    “Shown are the average ratios of three replica hybridizations.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other miRNAs are temporally expressed during development of the CNS and are repressed in the mature CNS.

    “other miRNAs are temporally expressed during development of the CNS being repressed in the mature CNS (Miska et al. 2004).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Miska et al. 2004 source

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Brain area-enriched miRNAs were identified by one-sample t-tests using pooled variances with a P-value threshold of 0.05.

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

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Altered miRNA profiles have been reported in the prefrontal cortex of patients with schizophrenia and schizoaffective disorder.

    “while another study has reported altered miRNA profiles in the prefrontal cortex of patients with schizophrenia and schizoaffective disorder (Perkins et al. 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Perkins et al. 2007 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    miR-124a expression can be detected in E11.5 mouse embryos and continues to be expressed in neurons of adult mice.

    “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)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Miska et al. 2004 source
    • cites Visvanathan et al. 2007 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Most animal miRNAs pair to the 3' UTRs of their targets by incomplete base-pairing, in which nucleotides 2-7 of the mature miRNA sequence, the seed region, appear critical for target site recognition.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lewis et al. 2005 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Conditional ablation of Dicer in murine post-mitotic Purkinje cells results in progressive loss of miRNAs, cerebellar degeneration, and development of ataxia.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schaefer et al. 2007 source

  • May combine two claims.

    Premisecitation

    Luciferase reporter assays have identified myotrophin (Mtpn) as a target of miR-124 regulation, both of which are highly expressed in neurons throughout the brain.

    “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).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Krek et al. 2005 source
    • cites Fujigasaki et al. 1996 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    miR-134 is present in dendrites, where it represses local synthesis of the protein kinase Limk1 to regulate spine size.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schratt et al. 2006 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Recent reports suggest that miRNAs can regulate dendritic spine size and neuronal morphogenesis, whereas massive parallel sequencing of small RNA libraries from human and chimpanzee brain has revealed highly complex miRNA repertoires in the primate brain.

    “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).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Schratt et al. 2006 source
    • cites Vo et al. 2005

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

    • cites Berezikov et al. 2006 source

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Background-subtracted spot intensities were normalized using variance stabilization normalization.

    “Background-subtracted spot intensities were normalized using variance stabilization normalization (Huber et al. 2002).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Huber et al. 2002 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    miR-125b is ubiquitously expressed in the brain and spinal cord of zebrafish, while its expression is confined to the mid-hindbrain boundary in the mouse.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ason et al. 2006

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

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationnone given

    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 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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    miR-1 is highly prevalent in the heart and skeletal muscle, whereas predicted targets of miR-1 are expressed at significantly lower levels in heart and skeletal muscle compared to other tissues.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sood et al. 2006 source

  • May combine two claims.

    Interpretationown data

    miR-34a, miR-204, and miR-205 might be coexpressed with their targets.

    “suggest that these miRNAs might be coexpressed with their targets.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Many miRNAs located within protein-coding and nonprotein-coding genes are transcriptionally linked to the expression of their host genes.

    “Many miRNAs located within protein-coding and nonprotein-coding genes are transcriptionally linked to the expression of their host genes (Rodriguez et al. 2004).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rodriguez et al. 2004 source

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    Relative expression was calculated using the DDC T method and normalized to the expression of snoRNA202.

    “Relative expression was calculated using the DDC T method (Livak and Schmittgen 2001) and normalized to the expression of snoRNA202 (Applied Biosystems).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Livak and Schmittgen 2001 source

      Queued — the background check reaches it, usually within a day.

    • Rests on an assumption: snoRNA202 is stably expressed across the adult mouse CNS regions studied.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the developing chick neural tube, miR-124a is a component of a regulatory network that controls the transition between neural progenitors and post-mitotic neurons by suppressing the anti-neural factor SCP1.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Visvanathan et al. 2007 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Maternal-zygotic dicer mutant zebrafish that lack all mature miRNAs display abnormal brain morphogenesis and neural differentiation.

    “Maternal-zygotic dicer mutant zebrafish that lack all mature miRNAs display abnormal brain morphogenesis and neural differentiation (Giraldez et al. 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Giraldez et al. 2005 source

      Queued — the background check reaches it, usually within a day.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Many neuronal miRNAs appear to be localized to actively translating polyribosomes in dendrites, where they may control localized translation of dendrite-specific mRNAs.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kim et al. 2004

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

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Stimulation of neurons relieves miR-134-mediated inhibition of Limk1 translation, which may contribute to synaptic plasticity.

    “Stimulation of neurons relieves miR-134-mediated inhibition of Limk1 translation, which, in turn, may contribute to synaptic plasticity (Schratt et al. 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schratt et al. 2006 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Injection of miR-430 rescues the brain defects in dicer mutant zebrafish embryos, inferring a general role in zebrafish brain morphogenesis.

    “Notably, injection of miR-430 rescues the brain defects in the mutant embryos, inferring a general role in zebrafish brain morphogenesis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Giraldez et al. 2005 source

      Queued — the background check reaches it, usually within a day.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Significance analysis of microarrays (SAM) was used to identify miRNAs differentially expressed between samples with a false discovery rate of 0.

    “Significance analysis of microarrays (SAM) was used to identify miRNAs differentially expressed between samples (FDR = 0) (Tusher et al. 2001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Tusher et al. 2001 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Expression profiling in adult tissues has identified miRNAs enriched in the CNS, suggesting that these miRNAs could play important regulatory roles in mature neurons.

    “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).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Babak et al. 2004

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

    • cites Barad et al. 2004 source
    • cites Miska et al. 2004 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Highly divergent expression patterns of conserved miRNAs in zebrafish, medaka, chicken, and mouse have previously been reported.

    “Highly divergent expression patterns of conserved miRNAs in zebrafish, medaka, chicken, and mouse have previously been reported (Ason et al. 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ason et al. 2006

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

  • Classified as probably not a substantial claim.

    Study design and conductnone given

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

    “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.”
    Quote in the paperSubstantial claim
50 of 50

  • The paper relies on this without support.

    Functional studies of miRNAs in the vertebrate nervous system are still very limited.

    “However, functional studies of miRNAs in the vertebrate nervous system are still very limited.”
    “Despite the accumulating evidence that miRNAs play important roles in brain development and disorders, our knowledge of miRNA function in the vertebrate nervous system is still very limited.”

  • The paper relies on this without support.

    The miRNA expression patterns observed in the dissected CNS regions of adult male Balb/c mice represent the adult mouse CNS generally.

    “To determine miRNA expression patterns in the adult mouse CNS, 13 different areas of the CNS were dissected from three male balb/c mice”
    “We present here an inventory of miRNA expression profiles from 13 neuroanatomically distinct areas of the adult mouse central nervous system (CNS).”

  • The paper relies on this without support.

    snoRNA202 is stably expressed across the adult mouse CNS regions studied.

    “normalized to the expression of snoRNA202 (Applied Biosystems).”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A previous large-scale analysis of miRNA expression across 13 distinct neuroanatomical regions lacked the resolution to describe miRNA expression on a cell type specific basis within nervous system tissues.

    “Bak and colleagues undertook a large scale analysis of miRNA expression across 13 distinct neuroanatomical regions, but lacked the resolution to describe miRNA expression on a cell type specific basis within these nervous system tissues8.”

    From CNS microRNA profiles: a database for cell type enriched microRNA expression across the mouse central nervous system (2020) · cites this paper as [8]

  • Using NGS methods combined with a greater sample size of each sex enabled identification of more expressed miRNAs than previous micro-array-based studies with up to 13 regions in male mice.

    “Previously, only micro-array-based studies were performed with up to 13 regions in male mice18,19. Using NGS methods combined with a greater sample size of each sex enabled us to identify more expressed miRNAs.”

    From A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase (2025) · cites this paper as [19]

  • A group of brain specific miRNAs, such as miR-124, miR-29b and miR-9, were highly enriched in all samples.

    “Consistent with previous reports, we observed that a group of miRNAs known to be brain specific, such as miR-124, miR-29b and miR-9, were highly enriched in all the samples. (Bak et al., 2008, Landgraf et al., 2007).”

    From Cell-Type-Based Analysis of MicroRNA Profiles in the Mouse Brain (2012) · cites this paper as Bak et al., 2008

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Seed region has two different nucleotide ranges

    Minor

    The text defines the miRNA seed region as nucleotides 2-7, while Table 1 defines it as nucleotides 2-8.

1 of 1

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Bak, M., Silahtaroglu, A., Møller, M., Christensen, M., Rath, M. F., Skryabin, B., Tommerup, N., & Kauppinen, S.
Affiliations
  • University of Copenhagen (DK)
  • University of Münster (DE)
ORCID
Venue
RNA
Publisher
Cold Spring Harbor Laboratory
Published
2008-01-29
Volume
14
Issue
3
Pages
432-444
ISSN
  • 1355-8382 (ISSN-L)
  • 1469-9001
DOI
10.1261/rna.783108
PMC
PMC2248253
OpenAlex
W2135920287
Semantic Scholar
7c288bee033438e69bcf9715205f6ffded1ef574
Cited by
463
References
54
Citations by year
2026: 2 · 2025: 7 · 2024: 11 · 2023: 12 · 2022: 29 · 2021: 12 · 2020: 21 · 2019: 33 · 2018: 27 · 2017: 33 · 2016: 26 · 2015: 45 · 2014: 31 · 2013: 42 · 2012: 30
FWCI
11.39
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • RNA (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Højteknologifonden
  • European Commission
  • National Research Foundation
  • Danmarks Grundforskningsfond
  • Lundbeckfonden
  • H. Lundbeck A/S
Topics
  • 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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
microRNA expression, central nervous system, miRNA expression profiling, post-transcriptional regulation, miRNA target mRNAs, gene regulatory networks, spinal cord, cerebellum, hippocampus, neocortex, olfactory bulb, pituitary gland, hypothalamus
MeSH terms
Animals, Central Nervous System, Male, Mice, Inbred BALB C, Species Specificity, Tissue Distribution, Zebrafish, Gene Expression, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, MicroRNAs, Mice

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-06.

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 ›

Are you an author, or do you see a problem with this page? Request a review