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A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay

J Cell Biol. 2005 Sep 12;170(6):913-24. doi: 10.1083/jcb.200504039.

Abstract

4E-transporter (4E-T) is one of several proteins that bind the mRNA 5'cap-binding protein, eukaryotic initiation factor 4E (eIF4E), through a conserved binding motif. We previously showed that 4E-T is a nucleocytoplasmic shuttling protein, which mediates the import of eIF4E into the nucleus. At steady state, 4E-T is predominantly cytoplasmic and is concentrated in bodies that conspicuously resemble the recently described processing bodies (P-bodies), which are believed to be sites of mRNA decay. In this paper, we demonstrate that 4E-T colocalizes with mRNA decapping factors in bona fide P-bodies. Moreover, 4E-T controls mRNA half-life, because its depletion from cells using short interfering RNA increases mRNA stability. The 4E-T binding partner, eIF4E, also is localized in P-bodies. 4E-T interaction with eIF4E represses translation, which is believed to be a prerequisite for targeting of mRNAs to P-bodies. Collectively, these data suggest that 4E-T interaction with eIF4E is a priming event in inducing messenger ribonucleoprotein rearrangement and transition from translation to decay.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Western
  • Cycloheximide / pharmacology
  • Eukaryotic Initiation Factor-4E / metabolism*
  • Fatty Acids, Unsaturated / pharmacology
  • Fluorescent Antibody Technique, Indirect
  • Fluorescent Dyes
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Inclusion Bodies / metabolism*
  • Luciferases / analysis
  • Luciferases / metabolism
  • Microscopy, Fluorescence
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Organic Chemicals
  • Protein Binding
  • Protein Synthesis Inhibitors / pharmacology
  • RNA Stability*
  • RNA, Small Interfering / metabolism
  • Xanthenes

Substances

  • Alexa594
  • EIF4ENIF1 protein, human
  • Eukaryotic Initiation Factor-4E
  • Fatty Acids, Unsaturated
  • Fluorescent Dyes
  • Nucleocytoplasmic Transport Proteins
  • Organic Chemicals
  • Protein Synthesis Inhibitors
  • RNA, Small Interfering
  • Xanthenes
  • Texas red
  • Cycloheximide
  • Luciferases
  • leptomycin B