title: The impact of microRNAs on protein output.
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.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: Daehyun
authors.initials: D
authors.lastname: Baek
authors.forename: Judit
authors.initials: J
authors.lastname: Villén
authors.forename: Chanseok
authors.initials: C
authors.lastname: Shin
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Camargo
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D040901:Proteomics; D014162:Transfection
chemical_list: D035683:MicroRNAs