title: CPEB2-eEF2 interaction impedes HIF-1α RNA translation.
abstract: Translation of mRNA into protein proceeds in three phases: initiation, elongation, and termination. Regulated translation allows the prompt production of selective proteins in response to physiological needs and is often controlled by sequence-specific RNA-binding proteins that function at initiation. Whether the elongation phase of translation can be modulated individually by trans-acting factors to synthesize polypeptides at variable rates remains to be determined. Here, we demonstrate that the RNA-binding protein, cytoplasmic polyadenylation element binding protein (CPEB)2, interacts with the elongation factor, eEF2, to reduce eEF2/ribosome-triggered GTP hydrolysis in vitro and slow down peptide elongation of CPEB2-bound RNA in vivo. The interaction of CPEB2 with eEF2 downregulates HIF-1α RNA translation under normoxic conditions; however, when cells encounter oxidative stress, CPEB2 dissociates from HIF-1α RNA, leading to rapid synthesis of HIF-1α for hypoxic adaptation. This study delineates the molecular mechanism of CPEB2-repressed translation and presents a unique model for controlling transcript-selective translation at elongation.
authors.affiliation: Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Po-Jen
authors.initials: PJ
authors.lastname: Chen
authors.forename: Yi-Shuian
authors.initials: YS
authors.lastname: Huang
mesh_terms: D000818:Animals; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats
chemical_list: C483243:CPEB2 protein, mouse; D015852:Eukaryotic Initiation Factor-2; C497443:Hif1a protein, mouse; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016601:RNA-Binding Proteins; D012313:RNA