p38-Dependent phosphorylation of the mRNA decay-promoting factor KSRP controls the stability of select myogenic transcripts

Paola Briata, Sonia Vanina Forcales, Marco Ponassi, Giorgio Corte, Ching Yi Chen, Michael Karin, Pier Lorenzo Puri, Roberto Gherzi

Research output: Contribution to journalArticle

Abstract

Transcriptional and posttranscriptional processes regulate expression of genetic networks in response to environmental cues. The extracellular signal-activated p38 MAP kinase (p38) pathway plays a fundamental role in conversion of myoblasts to differentiated myocytes. p38 phosphorylates specific transcription factors and chromatin-associated proteins promoting assembly of the myogenic transcriptome. Here, we demonstrate that p38 α and β isoforms also control muscle-gene expression posttranscriptionally, by stabilizing critical myogenic transcripts. KSRP, an important factor for AU-rich element (ARE)-directed mRNA decay, undergoes p38-dependent phosphorylation during muscle differentiation. KSRP phosphorylated by p38 displays compromised binding to ARE-containing transcripts and fails to promote their rapid decay, although it retains the ability to interact with the mRNA degradation machinery. Overexpression of KSRP selectively impairs induction of ARE-containing early myogenic transcripts, without affecting p38-mediated transcriptional responses. Our results uncover an unanticipated role for KSRP in establishing a biochemical link between differentiation-activated p38 signaling and turnover of myogenic mRNAs.

Original languageEnglish
Pages (from-to)891-903
Number of pages13
JournalMolecular Cell
Volume20
Issue number6
DOIs
Publication statusPublished - Dec 22 2005

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology

Cite this