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

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

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.

MeSH terms

  • 5' Untranslated Regions / genetics
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Base Sequence
  • Bcl-2-Like Protein 11 / genetics
  • Bcl-2-Like Protein 11 / metabolism
  • Cells, Cultured
  • Flow Cytometry
  • Gene Expression Profiling / methods
  • Gene Expression Regulation*
  • Immunoblotting
  • Mice, Knockout
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Protein Biosynthesis / genetics*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • 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
  • Transcriptome / genetics*

Substances

  • 5' Untranslated Regions
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • MIRN17-92 microRNA, mouse
  • MicroRNAs
  • Receptors, Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II