hnRNP A1 relocalization to the stress granules reflects a role in the stress response

Sonia Guil, Jennifer C Long, Javier F Cáceres

Research output: Contribution to journalArticlepeer-review

Abstract

hnRNP A1 is a nucleocytoplasmic shuttling protein that is involved in many aspects of mRNA metabolism. We have previously shown that activation of the p38 stress-signaling pathway in mammalian cells results in both hyperphosphorylation and cytoplasmic accumulation of hnRNP A1, affecting alternative splicing regulation in vivo. Here we show that the stress-induced cytoplasmic accumulation of hnRNP A1 occurs in discrete phase-dense particles, the cytoplasmic stress granules (SGs). Interestingly, mRNA-binding activity is required for both phosphorylation of hnRNP A1 and localization to SGs. We also show that these effects are mediated by the Mnk1/2 protein kinases that act downstream of p38. Finally, depletion of hnRNP A1 affects the recovery of cells from stress, suggesting a physiologically significant role for hnRNP A1 in the stress response. Our data are consistent with a model whereby hnRNP A1 recruitment to SGs involves Mnk1/2-dependent phosphorylation of mRNA-bound hnRNP A1.
Original languageEnglish
Pages (from-to)5744-58
Number of pages15
JournalMolecular and Cellular Biology
Volume26
Issue number15
DOIs
Publication statusPublished - Aug 2006

Keywords

  • Animals
  • Cell Survival
  • Cytoplasmic Granules
  • Enzyme Activation
  • HeLa Cells
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • NIH 3T3 Cells
  • Oxidative Stress
  • Peptides
  • Phosphorylation
  • Poly(A)-Binding Protein I
  • Poly(A)-Binding Proteins
  • Protein-Serine-Threonine Kinases
  • RNA Interference
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Signal Transduction

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