hnRNP A1 relocalization to the stress granules reflects a role in the stress response.
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.
Guil
Sonia
S
Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh, Scotland, United Kingdom.
Long
Jennifer C
JC
Cáceres
Javier F
JF
D000818:Animals; D002470:Cell Survival; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D018384:Oxidative Stress; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D039122:Poly(A)-Binding Protein I / Q000235:genetics / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000074019:T-Cell Intracellular Antigen-1
D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D039122:Poly(A)-Binding Protein I; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C491395:MKNK1 protein, human; C486342:MKNK2 protein, human; D017346:Protein Serine-Threonine Kinases