General RNA-binding proteins have a function in poly(A)-binding protein-dependent translation

EMBO J. 2009 Jan 7;28(1):58-68. doi: 10.1038/emboj.2008.259. Epub 2008 Dec 11.


The interaction between the poly(A)-binding protein (PABP) and eukaryotic translational initiation factor 4G (eIF4G), which brings about circularization of the mRNA, stimulates translation. General RNA-binding proteins affect translation, but their role in mRNA circularization has not been studied before. Here, we demonstrate that the major mRNA ribonucleoprotein YB-1 has a pivotal function in the regulation of eIF4F activity by PABP. In cell extracts, the addition of YB-1 exacerbated the inhibition of 80S ribosome initiation complex formation by PABP depletion. Rabbit reticulocyte lysate in which PABP weakly stimulates translation is rendered PABP-dependent after the addition of YB-1. In this system, eIF4E binding to the cap structure is inhibited by YB-1 and stimulated by a nonspecific RNA. Significantly, adding PABP back to the depleted lysate stimulated eIF4E binding to the cap structure more potently if this binding had been downregulated by YB-1. Conversely, adding nonspecific RNA abrogated PABP stimulation of eIF4E binding. These data strongly suggest that competition between YB-1 and eIF4G for mRNA binding is required for efficient stimulation of eIF4F activity by PABP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Extracts
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • Eukaryotic Initiation Factor-4F / metabolism*
  • Mice
  • Models, Biological
  • Nuclear Proteins / metabolism*
  • Poly(A)-Binding Proteins / metabolism*
  • Protein Biosynthesis*
  • Rabbits
  • Y-Box-Binding Protein 1


  • Cell Extracts
  • DNA-Binding Proteins
  • Eukaryotic Initiation Factor-4F
  • Nuclear Proteins
  • Poly(A)-Binding Proteins
  • Y-Box-Binding Protein 1
  • YBX1 protein, human