The non-stop decay mRNA surveillance pathway is required for oxidative stress tolerance

Nur Hidayah Jamar, Paraskevi Kritsiligkou, Chris M. Grant

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) are toxic by-products of normal aerobic metabolism. ROS can damage mRNAs and the translational apparatus resulting in translational defects and aberrant protein production. Three mRNA quality control systems monitor mRNAs for translational errors: nonsense-mediated decay, non-stop decay (NSD) and no-go decay (NGD) pathways. Here, we show that factors required for the recognition of NSD substrates and components of the SKI complex are required for oxidant tolerance. We found an overlapping requirement for Ski7, which bridges the interaction between the SKI complex and the exosome, and NGD components (Dom34/Hbs1) which have been shown to function in both NSD and NGD. We show that ski7 dom34 and ski7 hbs1 mutants are sensitive to hydrogen peroxide stress and accumulate an NSD substrate. We further show that NSD substrates are generated during ROS exposure as a result of aggregation of the Sup35 translation termination factor, which increases stop codon readthrough allowing ribosomes to translate into the 3- end of mRNAs. Overexpression of Sup35 decreases stop codon read-through and rescues oxidant tolerance consistent with this model. Our data reveal an unanticipated requirement for the NSD pathway during oxidative stress conditions which prevents the production of aberrant proteins from NSD mRNAs.

Original languageEnglish
Pages (from-to)6881-6893
Number of pages13
JournalNucleic Acids Research
Volume45
Issue number11
DOIs
Publication statusPublished - 1 Jun 2017

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RNA Stability
Oxidative Stress
Reactive Oxygen Species
Messenger RNA
Terminator Codon
Oxidants
Exosomes
Poisons
Ribosomes
Quality Control
Hydrogen Peroxide
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

The non-stop decay mRNA surveillance pathway is required for oxidative stress tolerance. / Jamar, Nur Hidayah; Kritsiligkou, Paraskevi; Grant, Chris M.

In: Nucleic Acids Research, Vol. 45, No. 11, 01.06.2017, p. 6881-6893.

Research output: Contribution to journalArticle

Jamar, Nur Hidayah ; Kritsiligkou, Paraskevi ; Grant, Chris M. / The non-stop decay mRNA surveillance pathway is required for oxidative stress tolerance. In: Nucleic Acids Research. 2017 ; Vol. 45, No. 11. pp. 6881-6893.
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