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c-Src-mediated phosphorylation of hnRNP K drives translational activation of specifically silenced mRNAs

Antje Ostareck-Lederer1, Dirk H Ostareck, Christophe Cans

  • 1European Molecular Biology Laboratory, Heidelberg, Germany. aostareck@anadyspharma.de

Molecular and Cellular Biology
|June 8, 2002
PubMed

Insights

Messenger RNA translation is silenced in immature cells and activated during maturation. This study reveals how the c-Src kinase phosphorylates hnRNP K, activating silenced messenger RNAs.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cellular Differentiation

Background:

  • Heterogeneous nuclear ribonucleoproteins (hnRNP K and hnRNP E1/E2) silence cellular and viral messenger RNAs (mRNAs) during cell differentiation.
  • The mechanisms for activating silenced mRNAs in maturing cells remain largely unknown.

Purpose of the Study:

  • To elucidate the mechanism by which silenced mRNAs become translationally activated during cellular maturation.
  • To identify the role of c-Src kinase in the translational regulation of specific mRNAs.

Main Methods:

  • Investigated the interaction between hnRNP K and c-Src kinase using in vivo and in vitro assays.
  • Analyzed the effect of c-Src-mediated phosphorylation on hnRNP K binding to the differentiation control element (DICE) of 15-lipoxygenase (LOX) mRNA.
  • Assessed the impact of this phosphorylation on the translation of DICE-bearing mRNAs in vivo.

Main Results:

  • hnRNP K and c-Src kinase were found to specifically interact, leading to c-Src activation and tyrosine phosphorylation of hnRNP K.
  • c-Src-mediated phosphorylation reversibly inhibited hnRNP K binding to the DICE in the 3' untranslated region of LOX mRNA.
  • This phosphorylation specifically derepressed the translation of DICE-bearing mRNAs in vivo.

Conclusions:

  • Established a novel role for c-Src kinase in the translational gene regulation of specific mRNAs.
  • Revealed a mechanism involving c-Src-mediated phosphorylation of hnRNP K that activates translationally silenced mRNAs during cellular differentiation.

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