Cited by 3,886MicroRNA in disease regulationRNA Research and SplicingPlant Molecular Biology Research

Mammalian microRNAs predominantly act to decrease target mRNA levels

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Guo, Huili, Ingolia, Nicholas T., Weissman, Jonathan S., Bartel, David P.·2010·Nature

Abstract

MicroRNAs (miRNAs) are endogenous approximately 22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (>/=84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.

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  • Global measurements indicate that miRNA targeting causes mostly mRNA destabilization, with translational repression comprising a detectable but minor component of overall repression.

    “Global measurements indicate that miRNA targeting causes mostly mRNA destabilization, with translational repression comprising a detectable but minor component of the overall repression33–36.”
  • When poly(A)-tail length is uncoupled from translational efficiency, the translational repression often detected as a minor component of overall repression arises from a mechanism different from the one that dominates pre-gastrulation.

    “We conclude that when poly(A)-tail length is uncoupled from TE, the translational repression often detected as a minor component of the overall repression33–35 arises from a mechanism different from the one that dominates pre-gastrulation.”

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Authors
Guo, H., Ingolia, N. T., Weissman, J. S., & Bartel, D. P.
Affiliations
  • Whitehead Institute for Biomedical Research (US)
  • QB3 (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Bartel, David P.
Venue
Nature
Published
2010-08
Volume
466
Issue
7308
Pages
835-840
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2133968430
Cited by
3,886
References
34
Citations by year
2026: 67 · 2025: 91 · 2024: 101 · 2023: 127 · 2022: 169 · 2021: 226 · 2020: 203 · 2019: 210 · 2018: 262 · 2017: 284 · 2016: 241 · 2015: 346 · 2014: 347 · 2013: 413 · 2012: 430
FWCI
121.41
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • PMC
Funders
  • Howard Hughes Medical Institute
  • Agency for Science, Technology and Research
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM067031, F32GM080853, GM080853)
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 stability, protein synthesis inhibition, mRNA cleavage, ribosome profiling, protein production, gene expression regulation
MeSH terms
Animals, HeLa Cells, Humans, Mammals, Models, Genetic, Ribosomes, RNA Processing, Post-Transcriptional, RNA, Messenger, Protein Biosynthesis, Down-Regulation, Open Reading Frames, 3' Untranslated Regions, RNA Stability, MicroRNAs, Mice

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