Assembly of an active translation initiation factor complex by a viral protein.
Recruitment of the 40S ribosome to the 5' end of a eukaryotic mRNA requires assembly of translation initiation factors eIF4E, the cap-binding protein, together with eIF4A and eIF4G into a complex termed eIF4F. While the translational repressor 4E-BP1 regulates binding of eIF4E to eIF4G, the forces required to construct an eIF4F complex remain unidentified. Here, we establish that the herpes simplex virus-1 (HSV-1) ICP6 polypeptide associates with eIF4G to promote eIF4F complex assembly. Strikingly, release of eIF4E from the 4E-BP1 repressor is insufficient to drive complex formation, suggesting that ICP6 is an eIF4F-assembly chaperone. This is the first example of a translation initiation factor-associated protein that promotes active complex assembly and defines a new, controllable step in the initiation of translation. Homology of the N-terminal, eIF4G-binding segment of ICP6 with cellular chaperones suggest that factors capable of interacting with eIF4G and promoting eIF4F complex assembly may play important roles in a variety of processes where translation complexes need to be remodeled or assembled on populations of newly synthesized or derepressed mRNAs, including development, differentiation, and the response to a broad spectrum of environmental cues.
Walsh
Derek
D
Department of Microbiology and New York University Cancer Institute, New York University School of Medicine, New York, New York 10016, USA.
Mohr
Ian
I
D002460:Cell Line; D002847:Chromatography, Agarose; D003001:Cloning, Molecular; D039562:Eukaryotic Initiation Factor-4F / Q000096:biosynthesis*; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D018832:Molecular Chaperones / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
D039562:Eukaryotic Initiation Factor-4F; D039603:Eukaryotic Initiation Factor-4G; D018832:Molecular Chaperones; D014764:Viral Proteins; C054366:herpes simplex virus type 1-protein ICP6