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

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 ana...

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Bibliographic Details
Published in:PLoS genetics 2017-02, Vol.13 (2), p.e1006623-e1006623
Main Authors: Jin, Hyun Yong, Oda, Hiroyo, Chen, Pengda, Yang, Chao, Zhou, Xiaojuan, Kang, Seung Goo, Valentine, Elizabeth, Kefauver, Jennifer M, Liao, Lujian, Zhang, Yaoyang, Gonzalez-Martin, Alicia, Shepherd, Jovan, Morgan, Gareth J, Mondala, Tony S, Head, Steven R, Kim, Pyeung-Hyeun, Xiao, Nengming, Fu, Guo, Liu, Wen-Hsien, Han, Jiahuai, Williamson, James R, Xiao, Changchun
Format: Article
Language:English
Subjects:
5' Untranslated Regions - genetics
Animals
B cells
B-Lymphocytes - cytology
B-Lymphocytes - metabolism
Base Sequence
Bcl-2-Like Protein 11 - genetics
Bcl-2-Like Protein 11 - metabolism
Binding sites
Biology
Biology and life sciences
Cells, Cultured
Colleges & universities
Flow Cytometry
Gene expression
Gene Expression Profiling - methods
Gene Expression Regulation
Genetic research
Genomics
Immunoblotting
Immunology
Investigations
Laboratories
Life sciences
Medicine and Health Sciences
Mice, Knockout
Mice, Transgenic
MicroRNA
MicroRNAs
MicroRNAs - genetics
Protein Biosynthesis - genetics
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Proteins
Receptor, Transforming Growth Factor-beta Type II
Receptors, Transforming Growth Factor beta - genetics
Receptors, Transforming Growth Factor beta - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Ribosomes - genetics
Ribosomes - metabolism
Rodents
Transcriptome - genetics
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Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1006623