Faculty Collaboration Database

Gene expression. MicroRNA control of protein expression noise. Science 2015 Apr 03;348(6230):128-32

Date

04/04/2015

Pubmed ID

25838385

DOI

10.1126/science.aaa1738

Scopus ID

2-s2.0-84928754032 (requires institutional sign-in at Scopus site)   293 Citations

Abstract

MicroRNAs (miRNAs) repress the expression of many genes in metazoans by accelerating messenger RNA degradation and inhibiting translation, thereby reducing the level of protein. However, miRNAs only slightly reduce the mean expression of most targeted proteins, leading to speculation about their role in the variability, or noise, of protein expression. We used mathematical modeling and single-cell reporter assays to show that miRNAs, in conjunction with increased transcription, decrease protein expression noise for lowly expressed genes but increase noise for highly expressed genes. Genes that are regulated by multiple miRNAs show more-pronounced noise reduction. We estimate that hundreds of (lowly expressed) genes in mouse embryonic stem cells have reduced noise due to substantial miRNA regulation. Our findings suggest that miRNAs confer precision to protein expression and thus offer plausible explanations for the commonly observed combinatorial targeting of endogenous genes by multiple miRNAs, as well as the preferential targeting of lowly expressed genes.

Author List

Schmiedel JM, Klemm SL, Zheng Y, Sahay A, Blüthgen N, Marks DS, van Oudenaarden A

Author

David S. Marks MD Vice Chair, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

3' Untranslated Regions
Animals
Embryonic Stem Cells
Gene Expression Regulation
Mice
MicroRNAs
Models, Genetic
Protein Biosynthesis
RNA, Messenger
Single-Cell Analysis
Transcription, Genetic