An mRNA-specific tRNA(i) carrier eIF2A plays a pivotal role in cell proliferation under stress conditions: stress-resistant translation of c-Src mRNA is mediated by eIF2A

作者:Kwon Oh Sung; An Sihyeon; Kim Eunah; Yu Jinbae; Hong Ka Young; Lee Jae Seung; Jang Sung Key*
来源:Nucleic Acids Research, 2017, 45(1): 296-310.
DOI:10.1093/nar/gkw1117

摘要

c-Src, a non-receptor protein tyrosine kinase, activates NF-kappa B and STAT3, which in turn triggers the transcription of anti-apoptosis-and cell cycle-related genes. c-Src protein regulates cell proliferation, cell motility and programmed cell death. And the elevated level of activated c-Src protein is related with solid tumor generation. Translation of c-Src mRNA is directed by an IRES element which mediates persistent translation under stress conditions when translation of most mRNAs is inhibited by a phosphorylation of the alpha subunit of eIF2 carrying the initiator tRNA (tRNA(i)) to 40S ribosomal subunit under normal conditions. The molecular basis of the stress-resistant translation of c-Src mRNA remained to be elucidated. Here, we report that eIF2A, an alternative tRNA(i) carrier, is responsible for the stress-resistant translation of c-Src mRNA. eIF2A facilitates tRNA(i) loading onto the 40S ribosomal subunit in a c-Src mRNA-dependent manner. And a direct interaction between eIF2A and a stem-loop structure (SL I) in the c-Src IRES is required for the c-Src IRES-dependent translation under stress conditions but not under normal conditions. Finally, we showed that the eIF2A-dependent translation of c-Src mRNA plays a pivotal role in cell proliferation under stress conditions.

  • 出版日期2017-1

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