Oxidation and alkylation stresses activate ribosome-quality control

• DOI: 10.1038/s41467-019-13579-3
• Publication Date: 2019-12-09T11:03:02Z
• Authors: Liewei L. Yan; Carrie L. Simms; Fionn McLoughlin; Richard D. Vierstra; Hani S. Zaher
• Keywords: Ribosomal Proteins; Saccharomyces cerevisiae Proteins; Alkylation; Science; RNA Stability; Saccharomyces cerevisiae; Quinolones; Article; DNA Adducts; Protein Aggregates; 03 medical and health sciences; Humans; RNA, Messenger; 0303 health sciences; Q; Methyl Methanesulfonate; 4-Nitroquinoline-1-oxide; Oxidative Stress; HEK293 Cells; Polyribosomes; Mutation; Peptides; Oxidation-Reduction; Ribosomes; DNA Damage

Oxidation and alkylation of nucleobases are known to disrupt their base-pairing properties within RNA. It is, however, unclear whether organisms have evolved general mechanism(s) deal with this damage. Here we show that the mRNA-surveillance pathway no-go decay associated ribosome-quality control activated in response nucleobase oxidation. Our findings reveal these processes important for clearing chemically modified mRNA resulting aberrant-protein products. In absence Xrn1, level damaged significantly increases. Furthermore, deletion LTN1 results accumulation protein aggregates presence oxidizing alkylating agents. This is accompanied by Hel2-dependent regulatory ubiquitylation ribosomal proteins. Collectively, our data highlight burden on cellular homeostasis suggest mechanisms counter accumulation.