title: Ribosome stalling regulates IRES-mediated translation in eukaryotes, a parallel to prokaryotic attenuation.
abstract: It was previously shown that the mRNA for the cat-1 Arg/Lys transporter is translated from an internal ribosome entry site (IRES) that is regulated by cellular stress. Amino acid starvation stimulated cat-1 translation via a mechanism that requires translation of an ORF in the mRNA leader and remodeling of the leader to form an active IRES (the "zipper model" of translational control). It is shown here that slowing of the leader peptide elongation rate, either by cycloheximide or the introduction of rare codons, stimulated translation of the downstream ORF. These results suggest that ribosome stalling in the upstream ORF causes mRNA remodeling and formation of an active IRES. This control is reminiscent of translation attenuation in prokaryotic operons, where inhibition of translation elongation can regulate both mRNA translation and gene transcription by altering mRNA structure.
authors.affiliation: Departments of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: James
authors.initials: J
authors.lastname: Fernandez
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yaman
authors.forename: Charles
authors.initials: C
authors.lastname: Huang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lopez
authors.forename: Anton A
authors.initials: AA
authors.lastname: Komar
authors.forename: Mark G
authors.initials: MG
authors.lastname: Caprara
authors.forename: William C
authors.initials: WC
authors.lastname: Merrick
authors.forename: Martin D
authors.initials: MD
authors.lastname: Snider
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Kaufman
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Lamers
authors.forename: Maria
authors.initials: M
authors.lastname: Hatzoglou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics; D002460:Cell Line; D018387:Codon, Initiator / Q000235:genetics; D018388:Codon, Terminator / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D010766:Phosphorylation; D011387:Prokaryotic Cells / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011817:Rabbits; D051381:Rats; D012270:Ribosomes / Q000378:metabolism*; D014162:Transfection
chemical_list: D027201:Cationic Amino Acid Transporter 1; D018387:Codon, Initiator; D018388:Codon, Terminator; D015852:Eukaryotic Initiation Factor-2; D012333:RNA, Messenger; D003513:Cycloheximide