Cited by 1,080MicroRNA in disease regulationRNA Research and SplicingPlant Molecular Biology Research

Animal MicroRNAs Confer Robustness to Gene Expression and Have a Significant Impact on 3′UTR Evolution

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Stark, Alexander, Brennecke, Julius, Bushati, Natascha, Russell, Robert B., Cohen, Stephen M.·2005·Cell

Abstract

MicroRNAs are small noncoding RNAs that serve as posttranscriptional regulators of gene expression in higher eukaryotes. Their widespread and important role in animals is highlighted by recent estimates that 20%-30% of all genes are microRNA targets. Here, we report that a large set of genes involved in basic cellular processes avoid microRNA regulation due to short 3'UTRs that are specifically depleted of microRNA binding sites. For individual microRNAs, we find that coexpressed genes avoid microRNA sites, whereas target genes and microRNAs are preferentially expressed in neighboring tissues. This mutually exclusive expression argues that microRNAs confer accuracy to developmental gene-expression programs, thus ensuring tissue identity and supporting cell-lineage decisions.

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Crossref · 10.1016/j.cell.2005.11.023

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  • The miRNAs in the first class are in line with studies showing that the expression level of predicted targets is generally higher before differentiation and that some miRNAs dampen output of transcriptionally down-regulated mRNAs to facilitate faster transition in gene expression.

    “The miRNAs in the first class are in line with studies showing that the expression level of the predicted targets is generally higher before differentiation, and that some miRNAs dampen the output of the transcriptionally down-regulated mRNAs to facilitate a faster transition in gene expression (Stark et al., 2005).”
  • As the silencing of loci is generally efficient, one might conclude that for most of the time in most mature neurons, some miRNAs are doing very little indeed, consistent with the idea that miRNAs confer robustness to programs of gene expression.

    “As the silencing of loci is generally efficient, one might conclude that for most of the time in most mature neurons, some miRNAs are doing very little indeed, consistent with the idea that miRNAs confer robustness to programs of gene expression [11,12].”
  • mRNAs from genes required for general cellular machinery are protected from miRNA action through possession of short 3' UTRs that are poor miRNA targets and genes required for specific cellular functions of the specific cell type are often miRNA anti-targets - that is, their 3' UTRs lack sequences that would enable binding of co-expressed miRNAs.

    “mRNAs from genes required for general cellular machinery are protected from miRNA action through possession of short 3' UTRs that are poor miRNA targets and genes required for specific cellular functions of the specific cell type are often miRNA anti-targets - that is, their 3' UTRs lack sequences that would enable binding of co-expressed miRNAs [12].”
  • Many examples of spatially exclusive expression domains of miRNAs and their targets have been documented.

    “For instance, in zebrafish, miR-430 targets a large number of maternally deposited transcripts at the onset of zygotic transcription [6] and many examples of spatially exclusive expression domains of miRNAs and their targets have been documented (for example, [12,53]).”
  • A common feature of miRNA function is mutually exclusive expression of miRNAs and their target mRNAs.

    “A common feature of miRNA function is one of mutually exclusive expression of miRNAs and their target mRNAs [11,12].”

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Authors
Stark, A., Brennecke, J., Bushati, N., Russell, R. B., & Cohen, S. M.
Affiliations
European Molecular Biology Laboratory (DE)
Corresponding author
Cohen, Stephen M.
Venue
Cell
Publisher
Elsevier BV
Published
2005-12
Volume
123
Issue
6
Pages
1133-1146
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2034500416
Cited by
1,080
References
53
Citations by year
2026: 4 · 2025: 17 · 2024: 14 · 2023: 21 · 2022: 15 · 2021: 38 · 2020: 20 · 2019: 29 · 2018: 37 · 2017: 34 · 2016: 30 · 2015: 51 · 2014: 68 · 2013: 88 · 2012: 82
FWCI
30.34
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
Keywords
microRNA, microRNA binding sites, post-transcriptional regulation, tissue-specific gene expression, co-expressed genes, cell lineage specification, tissue identity, non-coding RNA
MeSH terms
Animals, Base Sequence, Cell Line, Drosophila, Embryo, Nonmammalian, Membrane Proteins, Molecular Sequence Data, Muscles, Nerve Tissue Proteins, Nervous System, Nuclear Proteins, RNA, Messenger, Sequence Homology, Nucleic Acid, Tropomyosin, In Situ Hybridization, Homeodomain Proteins, Gene Expression Regulation, Developmental, Evolution, Molecular, 3' Untranslated Regions, Vacuolar Proton-Translocating ATPases, Drosophila Proteins, MicroRNAs, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins

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