CPEB2-eEF2 interaction impedes HIF-1α RNA translation

EMBO J. 2012 Feb 15;31(4):959-71. doi: 10.1038/emboj.2011.448. Epub 2011 Dec 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Eukaryotic Initiation Factor-2 / metabolism*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Protein Biosynthesis*
  • RNA / genetics*
  • RNA-Binding Proteins / metabolism*
  • Rats


  • CPEB2 protein, mouse
  • Eukaryotic Initiation Factor-2
  • Hif1a protein, mouse
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA-Binding Proteins
  • RNA

Associated data

  • GENBANK/JF973322
  • GENBANK/JF973323