title: An active role for the ribosome in determining the fate of oxidized mRNA.
abstract: Chemical damage to RNA affects its functional properties and thus may pose a significant hurdle to the translational apparatus; however, the effects of damaged mRNA on the speed and accuracy of the decoding process and their interplay with quality-control processes are not known. Here, we systematically explore the effects of oxidative damage on the decoding process using a well-defined bacterial in vitro translation system. We find that the oxidative lesion 8-oxoguanosine (8-oxoG) reduces the rate of peptide-bond formation by more than three orders of magnitude independent of its position within the codon. Interestingly, 8-oxoG had little effect on the fidelity of the selection process, suggesting that the modification stalls the translational machinery. Consistent with these findings, 8-oxoG mRNAs were observed to accumulate and associate with polyribosomes in yeast strains in which no-go decay is compromised. Our data provide compelling evidence that mRNA-surveillance mechanisms have evolved to cope with damaged mRNA.
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Simms
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Hudson
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Mosior
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Rangwala
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA. Electronic address: hzaher@wustl.edu.
authors.forename: Hani S
authors.initials: HS
authors.lastname: Zaher
mesh_terms: D002457:Cell Extracts; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D010084:Oxidation-Reduction; D010455:Peptides / Q000378:metabolism; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D002457:Cell Extracts; D010455:Peptides; D012333:RNA, Messenger; D006151:Guanosine; C046215:8-hydroxyguanosine