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

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dc.contributor.authorWilli, Jessica A.
dc.contributor.authorKüpfer, Pascal
dc.contributor.authorEvéquoz, Damien
dc.contributor.authorFernandez, Guillermo
dc.contributor.authorKatz, Assaf
dc.contributor.authorLeumann, Christian
dc.contributor.authorPolacek, Norbert
dc.date.accessioned2025-03-04T21:51:36Z
dc.date.available2025-03-04T21:51:36Z
dc.date.issued2018
dc.descriptionOpen access. Creative Commons Attribution-NonCommercial 4.0 International license (CC BY-NC 4.0) applies
dc.description.abstractIntracellular 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.
dc.description.peer-reviewYes
dc.identifier.citationWilli, J., Küpfer, P., Evéquoz, D., Fernandez, G., Katz, A., Leumann, C., & Polacek, N. (2018). Oxidative stress damages rRNA inside the ribosome and differentially affects the catalytic center. Nucleic Acids Research, 46(4), 1945-1957. https://doi.org/10.1093/nar/gkx1308
dc.identifier.urihttps://hdl.handle.net/10133/7020
dc.language.isoen
dc.publisherOxford Academic
dc.publisher.departmentDepartment of Chemistry & Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Bern
dc.publisher.institutionUniversidad de Chile
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.urlhttps://doi.org/10.1093/nar/gkx1308
dc.subjectRibosomal RNA
dc.subjectrRNA
dc.subjectRibosome oxidation
dc.subjectProtein synthesis
dc.subjectRNA oxidation
dc.subjectOxidative damage
dc.subject.lcshRibosomes--Research
dc.titleOxidative stress damages rRNA inside the ribosome and differentially affects the catalytic center
dc.typeArticle
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