A combinatorial code for CPE-mediated translational control

Cell. 2008 Feb 8;132(3):434-48. doi: 10.1016/j.cell.2007.12.038.

Abstract

Cytoplasmic polyadenylation plays a key role in the translational control of mRNAs driving biological processes such as gametogenesis, cell-cycle progression, and synaptic plasticity. What determines the distinct time of polyadenylation and extent of translational control of a given mRNA, however, is poorly understood. The polyadenylation-regulated translation is controlled by the cytoplasmic polyadenylation element (CPE) and its binding protein, CPEB, which can assemble both translational repression or activation complexes. Using a combination of mutagenesis and experimental validation of genome-wide computational predictions, we show that the number and relative position of two elements, the CPE and the Pumilio-binding element, with respect to the polyadenylation signal define a combinatorial code that determines whether an mRNA will be translationally repressed by CPEB, as well as the extent and time of cytoplasmic polyadenylation-dependent translational activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / metabolism*
  • Animals
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Cytoplasm / metabolism
  • Gene Expression Regulation*
  • Humans
  • Meiosis
  • Mice
  • Mutagenesis
  • Oocytes / metabolism
  • Polyadenylation* / drug effects
  • Progesterone / pharmacology
  • Protein Biosynthesis*
  • RNA 3' Polyadenylation Signals*
  • RNA, Messenger, Stored / metabolism
  • RNA-Binding Proteins / metabolism
  • Transcription Factors / metabolism
  • Xenopus Proteins / metabolism
  • Xenopus laevis
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • 3' Untranslated Regions
  • Cpeb1 protein, Xenopus
  • Cyclin B
  • PUM1 protein, Xenopus
  • RNA, Messenger, Stored
  • RNA-Binding Proteins
  • Transcription Factors
  • Xenopus Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • Progesterone