Cited by 344Cancer-related molecular mechanisms researchMicroRNA in disease regulationRNA Research and Splicing

Impact of MicroRNA levels, target-site complementarity, and cooperativity on competing endogenous RNA-regulated gene expression

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Denzler, Rémy, McGeary, Sean E., Title, Alexandra C., Agarwal, Vikram, Bartel, David P., Stoffel, Markus·2016·Molecular Cell

Abstract

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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Crossref · 10.1016/j.molcel.2016.09.027

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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).”

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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)
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
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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