Ribosome stalling regulates IRES-mediated translation in eukaryotes, a parallel to prokaryotic attenuation.
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.
Fernandez
James
J
Departments of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Yaman
Ibrahim
I
Huang
Charles
C
Liu
Haiyan
H
Lopez
Alex B
AB
Komar
Anton A
AA
Caprara
Mark G
MG
Merrick
William C
WC
Snider
Martin D
MD
Kaufman
Randal J
RJ
Lamers
Wouter H
WH
Hatzoglou
Maria
M
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
D027201:Cationic Amino Acid Transporter 1; D018387:Codon, Initiator; D018388:Codon, Terminator; D015852:Eukaryotic Initiation Factor-2; D012333:RNA, Messenger; D003513:Cycloheximide