Ribosome Stalling Regulates IRES-Mediated Translation in Eukaryotes, a Parallel to Prokaryotic Attenuation

Autor: Anton A. Komar, Randal J. Kaufman, James Fernandez, Martin D. Snider, Ibrahim Yaman, Mark G. Caprara, Haiyan Liu, Alex B. Lopez, William C. Merrick, Charles Huang, Wouter H. Lamers, Maria Hatzoglou
Přispěvatelé: AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Medical Biology, Anatomie en Embryologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism
Rok vydání: 2005
Předmět:
Zdroj: Molecular cell, 17(3), 405-416. Cell Press
Molecular Cell, 17(3), 405-416. Cell Press
ISSN: 1097-2765
DOI: 10.1016/j.molcel.2004.12.024
Popis: 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.
Databáze: OpenAIRE