title: Cellular mRNA recruits the ribosome via eIF3-PABP bridge to initiate internal translation.
abstract: IRES-mediated translation of key cell fate regulating genes has been implicated in tumorigenesis. Concerted action of canonical eukaryotic initiation factors and IRES transacting factors (ITAFs) was shown to regulate cellular IRES mediated translation; however, the precise molecular mechanism of ribosome recruitment to cellular IRESes remains unclear. Here we show that the X-linked inhibitor of apoptosis (XIAP) IRES operates in an evolutionary conserved viral like mode and the structural integrity, particularly in the vicinity of AUG, is critical for ribosome recruitment. The binding of eIF3 together with PABP potentiates ribosome recruitment to the IRES. Our data support the model in which eIF3 binds directly to the XIAP IRES RNA in a structure-dependent manner and acts as a scaffold for IRES RNA, PABP and the 40S ribosome.
authors.affiliation: a Apoptosis Research Center , Children's Hospital of Eastern Ontario Research Institute , Ottawa , Ontario , Canada.|c Department of Chemistry and Biochemistry , Alberta RNA Research and Training Institute, University of Lethbridge , Lethbridge , AB , Canada.
authors.forename: Nehal
authors.initials: N
authors.lastname: Thakor
authors.affiliation: d Department of Molecular and Cell Biology , University of California , Berkeley , CA , USA.
authors.forename: M Duane
authors.initials: MD
authors.lastname: Smith
authors.affiliation: c Department of Chemistry and Biochemistry , Alberta RNA Research and Training Institute, University of Lethbridge , Lethbridge , AB , Canada.
authors.forename: Luc
authors.initials: L
authors.lastname: Roberts
authors.affiliation: a Apoptosis Research Center , Children's Hospital of Eastern Ontario Research Institute , Ottawa , Ontario , Canada.
authors.forename: Mame Daro
authors.initials: MD
authors.lastname: Faye
authors.affiliation: c Department of Chemistry and Biochemistry , Alberta RNA Research and Training Institute, University of Lethbridge , Lethbridge , AB , Canada.
authors.forename: Harshil
authors.initials: H
authors.lastname: Patel
authors.affiliation: c Department of Chemistry and Biochemistry , Alberta RNA Research and Training Institute, University of Lethbridge , Lethbridge , AB , Canada.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Wieden
authors.affiliation: d Department of Molecular and Cell Biology , University of California , Berkeley , CA , USA.
authors.forename: Jamie H D
authors.initials: JHD
authors.lastname: Cate
authors.affiliation: a Apoptosis Research Center , Children's Hospital of Eastern Ontario Research Institute , Ottawa , Ontario , Canada.|b Department of Pediatrics , University of Ottawa , Ottawa , Ontario , Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Holcik
mesh_terms: D017209:Apoptosis; D018387:Codon, Initiator / Q000378:metabolism; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D000067556:Internal Ribosome Entry Sites; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D054682:Ribosome Subunits, Small, Eukaryotic / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D018387:Codon, Initiator; D039621:Eukaryotic Initiation Factor-3; D039642:Eukaryotic Initiation Factors; D000067556:Internal Ribosome Entry Sites; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human
keywords: Cellular IRES; NMIA-SHAPE; PABP; RNA structure; XIAP; eIF3; toeprinting assay
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