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PMID: 20703300 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Mammalian microRNAs predominantly act to decrease target mRNA levels.

Nature ·Vol. 466 ·No. 7308 ·2010-08-12 ·Pages 835-40

Guo H, Ingolia NT, Weissman JS, Bartel DP

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.

MeSH Terms
3' Untranslated Regions/genetics Animals Down-Regulation/genetics HeLa Cells Humans Mammals/genetics Mice MicroRNAs/genetics,metabolism Models, Genetic Open Reading Frames/genetics Protein Biosynthesis/genetics RNA Processing, Post-Transcriptional/genetics RNA Stability/genetics RNA, Messenger/analysis,genetics,metabolism Ribosomes/genetics,metabolism
Chemicals
3' Untranslated Regions MicroRNAs RNA, Messenger
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Guo Huili
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Ingolia Nicholas T
Weissman Jonathan S
Bartel David P
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34 references, click to expand
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature09267
Published
2010-08-12
Pages
835-40
Language
English
Region
England
NLM ID
0410462
PMCID
PMC2990499
Subset
IM
Grants
NIGMS NIH HHS · F32 GM080853 · United States
NIGMS NIH HHS · R01 GM067031-08 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM067031-06 · United States
NIGMS NIH HHS · GM080853 · United States
NIGMS NIH HHS · R01 GM067031 · United States
NIGMS NIH HHS · R01 GM067031-07 · United States
Databases
GEO
GSE22004
Corrections
CommentIn
PMID: 20733592
External Links
PubMed source DOI: 10.1038/nature09267 PMC Full Text View journal details
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