title: Alternative translation initiation of the Moloney murine leukemia virus mRNA controlled by internal ribosome entry involving the p57/PTB splicing factor.
abstract: Moloney murine leukemia virus (Mo-MuLV) genomic mRNA codes for two gag precursors by alternative initiations of translation. An AUG codon governs the synthesis of the retroviral capsid proteins precursor, whereas a CUG codon directs the synthesis of a glycosylated cell surface antigen, the gross cell surface antigen. Control of the relative synthesis of the two precursors is crucial for MuLV infectivity and pathology. Furthermore, the MuLV mRNA leader sequence is very long and should inhibit translation according to the classical scanning model. This suggests a different translation initiation mechanism allowing gag efficient expression. We demonstrate, by using bicistronic vectors expressed in COS-7 cells, that the Mo-MuLV mRNA leader drives translation initiation by internal ribosome entry. We have localized the internal ribosome entry site (IRES) between the two initiation codons. This 126 nucleotide long IRES implies an oligopyrimidine tract located 45 nucleotides upstream of AUG codon. UV cross-linking and affinity chromatography experiments show that the PTB/p57 splicing factor specifically interacts with this oligopyrimidine tract. The MuLV IRES controls alternative translation initiation by activating the capsid protein precursor expression. This gag translational enhancer could exist in other retroviruses.
authors.affiliation: INSERM U397, Endocrinologie et Communication Cellulaire, Institut Louis Bugnard, C.H.U. Rangueil, Toulouse, France.
authors.forename: S
authors.initials: S
authors.lastname: Vagner
authors.forename: A
authors.initials: A
authors.lastname: Waysbort
authors.forename: M
authors.initials: M
authors.lastname: Marenda
authors.forename: M C
authors.initials: MC
authors.lastname: Gensac
authors.forename: F
authors.initials: F
authors.lastname: Amalric
authors.forename: A C
authors.initials: AC
authors.lastname: Prats
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D003062:Codon; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005814:Genes, Viral; D007668:Kidney; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D010442:Peptide Chain Initiation, Translational; D016133:Polymerase Chain Reaction; D038941:Polypyrimidine Tract-Binding Protein; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D012367:RNA, Viral / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012270:Ribosomes / Q000378:metabolism* / Q000821:virology; D014158:Transcription, Genetic; D014162:Transfection; D015678:Viral Structural Proteins / Q000235:genetics
chemical_list: D003062:Codon; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D015678:Viral Structural Proteins; D038941:Polypyrimidine Tract-Binding Protein; D015500:Chloramphenicol O-Acetyltransferase