An mRNA-specific tRNAi carrier eIF2A plays a pivotal role in cell proliferation under stress conditions: Stress-resistant translation of c-Src mRNA is mediated by eIF2A
SCIE
SCOPUS
- Title
- An mRNA-specific tRNAi carrier eIF2A plays a pivotal role in cell proliferation under stress conditions: Stress-resistant translation of c-Src mRNA is mediated by eIF2A
- Authors
- KWON, OHSUNG; AN, SIHYEON; KIM, EUN AH; YU, JINBAE; HONG, KA YOUNG; LEE, JAE SEUNG; JANG, SUNG KEY
- Date Issued
- 2017-01
- Publisher
- Oxford University Press
- Abstract
- c-Src, a non-receptor protein tyrosine kinase, activates NF-��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 (tRNAi) 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 tRNAi carrier, is responsible for the stress-resistant translation of c-Src mRNA. eIF2A facilitates tRNAi loading onto the 40S ribosomal subunit in a c-Src mRNAdependent 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 eIF2Adependent translation of c-Src mRNA plays a pivotal role in cell proliferation under stress conditions. ? The Author(s) 2016.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/41290
- DOI
- 10.1093/nar/gkw1117
- ISSN
- 0305-1048
- Article Type
- Article
- Citation
- Nucleic Acids Research, vol. 45, no. 1, page. 296 - 310, 2017-01
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