Publication

Back to overview

Oxidative stress damages rRNA inside the ribosome and differentially affects the catalytic center

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Willi Jessica, Küpfer Pascal, Evéquoz Damien, Fernandez Guillermo, Katz Assaf, Leumann Christian, Polacek Norbert,
Project Stress-mediated effects on ribosome functions and translation control
Show all

Original article (peer-reviewed)

Journal Nucleic Acids Research
Volume (Issue) 46(4)
Page(s) 1945 - 1957
Title of proceedings Nucleic Acids Research
DOI 10.1093/nar/gkx1308

Open Access

URL http://doi.org/10.1093/nar/gkx1308
Type of Open Access Publisher (Gold Open Access)

Abstract

Intracellular levels of reactive oxygen species (ROS) increase as a consequence of oxidative stress and represent a major source of damage to biomolecules. Due to its high cellular abundance RNA is more frequently the target for oxidative damage than DNA. Nevertheless the functional consequences of damage on stable RNA are poorly understood. Using a genome-wide approach, based on 8-oxo-guanosine immunoprecipitation, we present evidence that the most abundant non-coding RNA in a cell, the ribosomal RNA (rRNA), is target for oxidative nucleobase damage by ROS. Subjecting ribosomes to oxidative stress, we demonstrate that oxidized 23S rRNA inhibits the ribosome during protein biosynthesis. Placing single oxidized nucleobases at specific position within the ribosome’s catalytic center by atomic mutagenesis resulted in markedly different functional outcomes. While some active site nucleobases tolerated oxidative damage well, oxidation at others had detrimental effects on protein synthesis by inhibiting different sub-steps of the ribosomal elongation cycle. Our data provide molecular insight into the biological consequences of RNA oxidation in one of the most central cellular enzymes and reveal mechanistic insight on the role of individual active site nucleobases during translation.
-