title: Enhancement of IRES-mediated translation of the c-myc and BiP mRNAs by the poly(A) tail is independent of intact eIF4G and PABP.
abstract: The poly(A) tail at the 3' end of mRNAs enhances 5' cap-dependent translation initiation. We show that it also enhances IRES-directed translation of two cellular mRNAs in vitro and in vivo. The underlying mechanisms, however, differ fundamentally. In contrast to cap-dependent translation, IRES-driven translation continues to be enhanced by the poly(A) tail following proteolytic cleavage of eIF4G. Moreover, the poly(A) tail stimulates IRES-mediated translation even in the presence of PAIP2 or following effective depletion of the poly(A) binding protein (PABP) from HeLa cell extracts. The PABP-eIF4G bridging complex that is critical for cap-dependent translation is thus dispensable for the enhancement of the IRESs by the poly(A) tail. The polyadenylated mRNA translation from cellular IRESs is also profoundly sensitive to eIF4A activity in vitro. These mechanistic and molecular distinctions implicate the potential for a new layer of translational control mechanisms.
authors.affiliation: EMBL Heidelberg, Gene Expression Programme, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thoma
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bergamini
authors.forename: Bruno
authors.initials: B
authors.lastname: Galy
authors.forename: Patrick
authors.initials: P
authors.lastname: Hundsdoerfer
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Hentze
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western; D002457:Cell Extracts; D004926:Escherichia coli / Q000235:genetics; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D039102:Poly(A)-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D002457:Cell Extracts; D039603:Eukaryotic Initiation Factor-4G; D039102:Poly(A)-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011994:Recombinant Proteins