Title

An Active Role for the Ribosome in Determining the Fate of Oxidized mRNA

Authors

Carrie L. Simms
Benjamin H. Hudson
John W. Mosior
Ali S. Rangwala
Hani S. ZaherFollow

Author's School

Arts & Sciences

Author's Department

Biology

Document Type

Article

Publication Date

11-20-2014

Originally Published In

Cell Rep. 2014 Nov 20;9(4):1256–1264. doi: 10.1016/j.celrep.2014.10.042

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.

Comments

This is an open access article under the CC BY-NC-ND license. Original is available at DOI: 10.1016/j.celrep.2014.10.042

Recommended Citation

Simms, Carrie L.; Hudson, Benjamin H.; Mosior, John W.; Rangwala, Ali S.; and Zaher, Hani S., "An Active Role for the Ribosome in Determining the Fate of Oxidized mRNA" (2014). Biology Faculty Publications & Presentations. 53.
https://openscholarship.wustl.edu/bio_facpubs/53