Cited by 3,592MicroRNA in disease regulationRNA Research and SplicingPlant Molecular Biology Research

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The impact of microRNAs on protein output

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Baek, Daehyun, Villén, Judit, Shin, Chanseok, Camargo, Fernando D., Gygi, Steven P., Bartel, David P.·2008·Nature

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Abstract

MicroRNAs are endogenous approximately 23-nucleotide RNAs that can pair to sites in the messenger RNAs of protein-coding genes to downregulate the expression from these messages. MicroRNAs are known to influence the evolution and stability of many mRNAs, but their global impact on protein output had not been examined. Here we use quantitative mass spectrometry to measure the response of thousands of proteins after introducing microRNAs into cultured cells and after deleting mir-223 in mouse neutrophils. The identities of the responsive proteins indicate that targeting is primarily through seed-matched sites located within favourable predicted contexts in 3' untranslated regions. Hundreds of genes were directly repressed, albeit each to a modest degree, by individual microRNAs. Although some targets were repressed without detectable changes in mRNA levels, those translationally repressed by more than a third also displayed detectable mRNA destabilization, and, for the more highly repressed targets, mRNA destabilization usually comprised the major component of repression. The impact of microRNAs on the proteome indicated that for most interactions microRNAs act as rheostats to make fine-scale adjustments to protein output.

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Authors: Baek, D., Villén, J., Shin, C., Camargo, F. D., Gygi, S. P., & Bartel, D. P.
Affiliations: Whitehead Institute for Biomedical Research (US)
Harvard University (US)
Howard Hughes Medical Institute (US)
Corresponding author: Gygi, Steven P.
Bartel, David P.
ORCID: Villén, Judit
Shin, Chanseok
Camargo, Fernando D.
Gygi, Steven P.
Bartel, David P.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2008-07-30
Volume: 455
Issue: 7209
Pages: 64-71
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature07242
PMC: PMC2745094
OpenAlex: W1988163167
Cited by: 3,592
References: 50
Citations by year: 2026: 39 · 2025: 65 · 2024: 82 · 2023: 98 · 2022: 137 · 2021: 138 · 2020: 140 · 2019: 150 · 2018: 164 · 2017: 198 · 2016: 208 · 2015: 257 · 2014: 287 · 2013: 328 · 2012: 342
FWCI: 108.87
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Howard Hughes Medical Institute
Damon Runyon Cancer Research Foundation
National Human Genome Research Institute (R01HG003456)
National Institute of General Medical Sciences (R01GM067031)
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, protein production, protein synthesis inhibition, mRNA destabilization, 3' untranslated region, miR-223, neutrophils, gene expression regulation, SILAC
MeSH terms: Animals, Gene Expression Regulation, HeLa Cells, Humans, Isotope Labeling, Male, Neutrophils, Transfection, Protein Biosynthesis, Oligonucleotide Array Sequence Analysis, MicroRNAs, Proteomics, Mice

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