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.
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 tRNAicarrier, is responsible for the stress-resistant translation of c-Src mRNA. eIF2A facilitates tRNAiloading 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.
authors.affiliation: Molecular Virology Laboratory, POSTECH Biotech Center, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Oh Sung
authors.initials: OS
authors.lastname: Kwon
authors.affiliation: Molecular Virology Laboratory, POSTECH Biotech Center, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Sihyeon
authors.initials: S
authors.lastname: An
authors.affiliation: Molecular Virology Laboratory, POSTECH Biotech Center, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Eunah
authors.initials: E
authors.lastname: Kim
authors.affiliation: Molecular Virology Laboratory, POSTECH Biotech Center, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Jinbae
authors.initials: J
authors.lastname: Yu
authors.affiliation: Molecular Virology Laboratory, POSTECH Biotech Center, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Ka Young
authors.initials: KY
authors.lastname: Hong
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Molecular Virology Laboratory, POSTECH Biotech Center, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea skjang0@gmail.com.|Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Sung Key
authors.initials: SK
authors.lastname: Jang
mesh_terms: D019921:Biotinylation; D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D012358:RNA, Transfer, Met / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements; D054682:Ribosome Subunits, Small, Eukaryotic / Q000737:chemistry / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D014415:Tunicamycin / Q000494:pharmacology; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D015852:Eukaryotic Initiation Factor-2; D016328:NF-kappa B; D012358:RNA, Transfer, Met; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014415:Tunicamycin; D012313:RNA; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human