Impact of MicroRNA levels, target-site complementarity, and cooperativity on competing endogenous RNA-regulated gene expression
Open accessAbstract
Expression changes of competing endogenous RNAs (ceRNAs) have been proposed to influence microRNA (miRNA) activity and thereby regulate other transcripts containing miRNA-binding sites. Here, we find that although miRNA levels define the extent of repression, they have little effect on the magnitude of the ceRNA expression change required to observe derepression. Canonical 6-nt sites, which typically mediate modest repression, can nonetheless compete for miRNA binding, with potency ∼20% of that observed for canonical 8-nt sites. In aggregate, low-affinity/background sites also contribute to competition. Sites with extensive additional complementarity can appear as more potent, but only because they induce miRNA degradation. Cooperative binding of proximal sites for the same or different miRNAs does increase potency. These results provide quantitative insights into the stoichiometric relationship between miRNAs and target abundance, target-site spacing, and affinity requirements for ceRNA-mediated gene regulation, and the unusual circumstances in which ceRNA-mediated gene regulation might be observed.
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mRNAs with higher affinity MREs generally show greater sensitivity to miRNA-mediated post-transcriptional repression.
“On the other hand, mRNAs with higher affinity MREs generally show greater sensitivity to miRNA-mediated post-transcriptional repression (84, 94).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [94]
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- Authors
- Denzler, R., McGeary, S. E., Title, A. C., Agarwal, V., Bartel, D. P., & Stoffel, M.
- Affiliations
- ETH Zurich (CH)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Bartel, David P.
- Stoffel, Markus
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 64
- Issue
- 3
- Pages
- 565-579
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5101187
- OpenAlex
- W2544684176
- Cited by
- 340
- References
- 36
- Citations by year
- 2026: 28 · 2025: 13 · 2024: 25 · 2023: 20 · 2022: 31 · 2021: 45 · 2020: 41 · 2019: 46 · 2018: 52 · 2017: 36 · 2016: 2 · 2014: 1
- FWCI
- 18.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc-nd)
- Elsevier eBooks
- ETH Zürich Research Collection
- Funders
- NIH (GM067031)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- 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
- Keywords
- competing endogenous RNA, microRNA, microRNA binding sites, miRNA degradation
- MeSH terms
- Red Fluorescent Protein, Adenoviridae, Animals, Bacterial Proteins, Binding Sites, Binding, Competitive, Gene Expression Regulation, Luminescent Proteins, Male, Mice, Inbred C57BL, Plasmids, RNA, Messenger, Transformation, Genetic, Genes, Reporter, Hepatocytes, MicroRNAs, Mice, Gene Regulatory Networks, Primary Cell Culture
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