A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay.
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.
Ferraiuolo
Maria A
MA
Department of Biochemistry, McGill University, Montréal, Québec H3G 1Y6, Canada.
Basak
Sanjukta
S
Dostie
Josee
J
Murray
Elizabeth L
EL
Schoenberg
Daniel R
DR
Sonenberg
Nahum
N
D015153:Blotting, Western; D003513:Cycloheximide / Q000494:pharmacology; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D008156:Luciferases / Q000032:analysis / Q000378:metabolism; D008856:Microscopy, Fluorescence; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D009930:Organic Chemicals; D011485:Protein Binding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000378:metabolism; D014966:Xanthenes
C417664:Alexa594; C411571:EIF4ENIF1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D029543:Nucleocytoplasmic Transport Proteins; D009930:Organic Chemicals; D011500:Protein Synthesis Inhibitors; D034741:RNA, Small Interfering; D014966:Xanthenes; C034657:Texas red; D003513:Cycloheximide; D008156:Luciferases; C038753:leptomycin B