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Nucleic Acids Res. 2017 Jan 9;45(1):296-310. doi: 10.1093/nar/gkw1117. Epub 2016 Nov 28.

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.

Author information

1
Molecular Virology Laboratory, POSTECH Biotech Center, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
2
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea.
3
Molecular Virology Laboratory, POSTECH Biotech Center, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea skjang0@gmail.com.

Abstract

c-Src, a non-receptor protein tyrosine kinase, activates NF-κB 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 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.

PMID:
27899592
PMCID:
PMC5224483
DOI:
10.1093/nar/gkw1117
[Indexed for MEDLINE]
Free PMC Article

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