Format

Send to

Choose Destination
PLoS Genet. 2017 Feb 27;13(2):e1006623. doi: 10.1371/journal.pgen.1006623. eCollection 2017 Feb.

Differential Sensitivity of Target Genes to Translational Repression by miR-17~92.

Author information

1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
2
Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, California, United States of America.
3
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
4
Division of Biomedical Convergence/Institute of Bioscience & Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
5
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
6
Shanghai Key Laboratory of Regulatory Biology, Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Life Sciences, East China Normal University, Shanghai, China.
7
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
8
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, United States of America.
9
Next Generation Sequencing Core, The Scripps Research Institute, La Jolla, California, United States of America.
10
Department of Molecular Bioscience/Institute of Bioscience & Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.

Abstract

MicroRNAs (miRNAs) are thought to exert their functions by modulating the expression of hundreds of target genes and each to a small degree, but it remains unclear how small changes in hundreds of target genes are translated into the specific function of a miRNA. Here, we conducted an integrated analysis of transcriptome and translatome of primary B cells from mutant mice expressing miR-17~92 at three different levels to address this issue. We found that target genes exhibit differential sensitivity to miRNA suppression and that only a small fraction of target genes are actually suppressed by a given concentration of miRNA under physiological conditions. Transgenic expression and deletion of the same miRNA gene regulate largely distinct sets of target genes. miR-17~92 controls target gene expression mainly through translational repression and 5'UTR plays an important role in regulating target gene sensitivity to miRNA suppression. These findings provide molecular insights into a model in which miRNAs exert their specific functions through a small number of key target genes.

PMID:
28241004
PMCID:
PMC5348049
DOI:
10.1371/journal.pgen.1006623
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center