Animal MicroRNAs Confer Robustness to Gene Expression and Have a Significant Impact on 3′UTR Evolution
Open accessAbstract
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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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).”
From Identification of Dynamically Regulated MicroRNA and mRNA Networks in Developing Oligodendrocytes (2008) · cites this paper as 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].”
From MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system (2007) · cites this paper as [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].”
From MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system (2007) · cites this paper as [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]).”
From MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system (2007) · cites this paper as [12]
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].”
From MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system (2007) · cites this paper as [12]
This profile is one of the best conserved miRNA patterns, as a similar restriction to mature neurons is seen for mouse and fly miR-124.
“This profile is one of the best conserved miRNA patterns, as a similar restriction to mature neurons is seen for mouse and fly miR-124 [12,30].”
From MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system (2007) · cites this paper as [12]
Changes in miRNA expression levels can tip the balance and result in repression or activation of target genes.
“A change in the expression levels of miRNAs can tip the balance and result in repression or activation of many functionally important target genes101,102.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [101]
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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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2821 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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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