title: A new translational regulator with homology to eukaryotic translation initiation factor 4G.
abstract: Translation initiation in eukaryotes is facilitated by the cap structure, m7GpppN (where N is any nucleotide). Eukaryotic translation initiation factor 4F (eIF4F) is a cap binding protein complex that consists of three subunits: eIF4A, eIF4E and eIF4G. eIF4G interacts directly with eIF4E and eIF4A. The binding site of eIF4E resides in the N-terminal third of eIF4G, while eIF4A and eIF3 binding sites are present in the C-terminal two-thirds. Here, we describe a new eukaryotic translational regulator (hereafter called p97) which exhibits 28% identity to the C-terminal two-thirds of eIF4G. p97 mRNA has no initiator AUG and translation starts exclusively at a GUG codon. The GUG-initiated open reading frame (907 amino acids) has no canonical eIF4E binding site. p97 binds to eIF4A and eIF3, but not to eIF4E. Transient transfection experiments show that p97 suppresses both cap-dependent and independent translation, while eIF4G supports both translation pathways. Furthermore, inducible expression of p97 reduces overall protein synthesis. These results suggest that p97 functions as a general repressor of translation by forming translationally inactive complexes that include eIF4A and eIF3, but exclude eIF4E.
authors.affiliation: Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Imataka
authors.forename: H S
authors.initials: HS
authors.lastname: Olsen
authors.forename: N
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D003001:Cloning, Molecular; D018387:Codon, Initiator / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004686:Encephalomyocarditis virus / Q000235:genetics; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000378:metabolism; D010920:Placenta; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
chemical_list: D018387:Codon, Initiator; D018076:DNA, Complementary; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; C104836:eukaryotic translational regulator p97