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The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution
Abstract
Thousands of mammalian messenger RNAs are under selective pressure to maintain 7-nucleotide sites matching microRNAs (miRNAs). We found that these conserved targets are often highly expressed at developmental stages before miRNA expression and that their levels tend to fall as the miRNA that targets them begins to accumulate. Nonconserved sites, which outnumber the conserved sites 10 to 1, also mediate repression. As a consequence, genes preferentially expressed at the same time and place as a miRNA have evolved to selectively avoid sites matching the miRNA. This phenomenon of selective avoidance extends to thousands of genes and enables spatial and temporal specificities of miRNAs to be revealed by finding tissues and developmental stages in which messages with corresponding sites are expressed at lower levels.
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In the citing paper
“This cellular prevalence of negative correlation signatures is in agreement with other genome-wide studies showing that the predicted targets are expressed at lower levels in tissues where the miRNA is present compared to other tissues where the miRNA is absent (Farh et al., 2005).”
From Identification of Dynamically Regulated MicroRNA and mRNA Networks in Developing Oligodendrocytes (2008) · cites this paper as Farh et al., 2005
In the citing 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.”
From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Farh et al. 2005
In the citing paper
“We also find miR-10a and miR-10b to be enriched in both medulla oblongata and spinal cord, which is consistent with their predicted accumulation in the lower spinal cord (Farh et al. 2005).”
From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Farh et al. 2005
In the citing paper
“Consistent with previous reports, we found that miR-7 and miR-7b were enriched in the pituitary and hypothalamus (Farh et al. 2005);”
From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Farh et al. 2005
In the citing paper
“Previous computational analyses of microarray data have shown that predicted mRNA targets of several highly tissue-specific miRNAs are expressed at significantly lower levels in the same tissues compared to tissues where such miRNAs are not expressed (Farh et al. 2005;Sood et al. 2006).”
From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Farh et al. 2005
In the citing paper
“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 [11]
In the citing paper
“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 [11]
In the citing paper
“Notably, significantly enriched motifs among these lesser abundant seeds include those corresponding to miRNAs previously described as brain-enriched (e.g., miR-101, miR-153, and miR-485) or having synaptic (e.g., miR-138) or glial (e.g., miR-23) localization (Cohen et al., 2011; Farh et al., 2005; Lagos-Quintana et al., 2002; Sempere et al., 2004; Siegel et al., 2009; Smirnova et al., 2005), sign”
From Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain (2014) · cites this paper as Farh et al., 2005
In the citing paper
“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 [102]
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Metadata
- Authors
- Farh, K. K.-H., Grimson, A., Jan, C., Lewis, B. P., Johnston, W. K., Lim, L. P., Burge, C. B., & Bartel, D. P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Farh, Kyle Kai-How
- Grimson, Andrew
- Bartel, David P.
- ORCID
- Venue
- Science
- Published
- 2005-12-16
- Volume
- 310
- Issue
- 5755
- Pages
- 1817-1821
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1990868443
- Cited by
- 1,484
- References
- 23
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 21 · 2023: 33 · 2022: 31 · 2021: 29 · 2020: 63 · 2019: 45 · 2018: 65 · 2017: 63 · 2016: 61 · 2015: 99 · 2014: 106 · 2013: 92 · 2012: 99
- FWCI
- 36.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (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, mRNA repression, microRNA binding sites, selective avoidance, gene expression evolution, developmental gene expression, mammalian gene regulation
- MeSH terms
- Animals, Base Sequence, Cell Differentiation, Gene Expression Regulation, Humans, Mammals, Molecular Sequence Data, Organ Specificity, RNA, Messenger, Species Specificity, Zebrafish, Conserved Sequence, Muscle Fibers, Skeletal, Evolution, Molecular, Untranslated Regions, Gene Expression Profiling, RNA Stability, MicroRNAs, Mice, Rats
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