title: Direct ribosomal binding by a cellular inhibitor of translation.
abstract: During apoptosis and under conditions of cellular stress, several signaling pathways promote inhibition of cap-dependent translation while allowing continued translation of specific messenger RNAs encoding regulatory and stress-response proteins. We report here that the apoptotic regulator Reaper inhibits protein synthesis by binding directly to the 40S ribosomal subunit. This interaction does not affect either ribosomal association of initiation factors or formation of 43S or 48S complexes. Rather, it interferes with late initiation events upstream of 60S subunit joining, apparently modulating start-codon recognition during scanning. CrPV IRES-driven translation, involving direct ribosomal recruitment to the start site, is relatively insensitive to Reaper. Thus, Reaper is the first known cellular ribosomal binding factor with the potential to allow selective translation of mRNAs initiating at alternative start codons or from certain IRES elements. This function of Reaper may modulate gene expression programs to affect cell fate.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Colón-Ramos
authors.forename: Christina L
authors.initials: CL
authors.lastname: Shenvi
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Weitzel
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Gan
authors.forename: Robert
authors.initials: R
authors.lastname: Matts
authors.forename: Jamie
authors.initials: J
authors.lastname: Cate
authors.forename: Sally
authors.initials: S
authors.lastname: Kornbluth
mesh_terms: D000818:Animals; D001692:Biological Transport; D018387:Codon, Initiator / Q000235:genetics; D004260:DNA Repair; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D018387:Codon, Initiator; D029721:Drosophila Proteins; D012333:RNA, Messenger; C086973:rpr protein, Drosophila