Promoter-Dependent Translation Controlled by p54nrb and hnRNPM during Myoblast Differentiation

PLoS One. 2015 Sep 2;10(9):e0136466. doi: 10.1371/journal.pone.0136466. eCollection 2015.

Abstract

Fibroblast growth factor 1 (FGF1) is induced during myoblast differentiation at both transcriptional and translational levels. Here, we identify hnRNPM and p54nrb/NONO present in protein complexes bound to the FGF1 promoter and to the mRNA internal ribosome entry site (IRES). Knockdown or overexpression of these proteins indicate that they cooperate in activating IRES-dependent translation during myoblast differentiation, in a promoter-dependent manner. Importantly, mRNA transfection and promoter deletion experiments clearly demonstrate the impact of the FGF1 promoter on the activation of IRES-dependent translation via p54nrb and hnRNPM. Accordingly, knockdown of either p54 or hnRNPM also blocks endogenous FGF1 induction and myotube formation, demonstrating the physiological relevance of this mechanism and the role of these two proteins in myogenesis. Our study demonstrates the cooperative function of hnRNPM and p54nrb as regulators of IRES-dependent translation and indicates the involvement of a promoter-dependent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • DNA-Binding Proteins
  • Fibroblast Growth Factor 1 / genetics*
  • Heterogeneous-Nuclear Ribonucleoprotein Group M / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group M / metabolism*
  • Internal Ribosome Entry Sites*
  • Mice
  • Myoblasts / cytology*
  • Myoblasts / metabolism
  • Nuclear Matrix-Associated Proteins / genetics
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Octamer Transcription Factors / genetics
  • Octamer Transcription Factors / metabolism*
  • Promoter Regions, Genetic*
  • Protein Binding
  • Protein Biosynthesis*
  • Protein Interaction Mapping
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*

Substances

  • DNA-Binding Proteins
  • HNRNPM protein, human
  • Heterogeneous-Nuclear Ribonucleoprotein Group M
  • Internal Ribosome Entry Sites
  • NONO protein, human
  • Nuclear Matrix-Associated Proteins
  • Octamer Transcription Factors
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Fibroblast Growth Factor 1

Grant support

This work has been funded by Association Française contre les Myopathies (grant 16966), Association pour la Recherche sur le Cancer (grant PJA-20131200230), Ligue pour la Recherche Contre le Cancer, Cancéropole Grand Sud-Ouest, Institut National du Cancer (grant RIBOCAN no. 2008-039), Fondation de l’Avenir (grant ET0-583), Région Midi-Pyrénées (grant 11052677), Fonds Européen du Développement Régional (grant REFBIO-VEMT). There was no commercial funder. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.