c-Src activates endonuclease-mediated mRNA decay.
The mRNA endonuclease PMR1 initiates mRNA decay by forming a selective complex with its translating substrate mRNA. Previous work showed that the ability of PMR1 to target to polysomes and activate decay depends on the phosphorylation of a tyrosine residue at position 650. The current study shows that c-Src is responsible for activating this mRNA decay pathway. c-Src was recovered with immunoprecipitated PMR1, and it phosphorylates PMR1 in vitro and in vivo. The interaction with c-Src involves two domains of PMR1: Y650 and a series of proline-rich SH3 peptides in the N terminus. In cells with little c-Src, PMR1 targeting to polysomes is induced by constitutively active c-Src but not by inactive forms of the kinase. Similarly, only active c-Src induces PMR1-mediated mRNA decay. Finally, we show that EGF rapidly induces c-Src phosphorylation of PMR1, providing a direct link between tyrosine kinase-mediated signal transduction and mRNA decay.
Peng
Yong
Y
Department of Molecular and Cellular Biochemistry, The RNA Group and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Schoenberg
Daniel R
DR
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002384:Catalysis; D002522:Chlorocebus aethiops; D004720:Endonucleases / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism*; D004789:Enzyme Activation; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011132:Polyribosomes / Q000378:metabolism; D011485:Protein Binding; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D014981:Xenopus / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D018909:src Homology Domains
D050505:Mutant Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; D019000:Phosphotyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D004720:Endonucleases; D004722:Endoribonucleases; C116181:polysomal RNase 1