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

Willi, Jessica; Küpfer, Pascal; Evéquoz, Damien; Fernandez, Guillermo; Katz, Assaf; Leumann, Christian; Polacek, Norbert (2018). Oxidative stress damages rRNA inside the ribosome and differentially affects the catalytic center. Nucleic acids research, 46(4), pp. 1945-1957. Information Retrieval Ltd. 10.1093/nar/gkx1308

[img]
Preview
Text
Willi_NAR_2018.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC).

Download (4MB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Willi, Jessica; Küpfer, Pascal; Evéquoz, Damien; Leumann, Christian and Polacek, Norbert

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

0305-1048

Publisher:

Information Retrieval Ltd.

Language:

English

Submitter:

Christina Schüpbach

Date Deposited:

26 Jan 2018 16:49

Last Modified:

12 Nov 2019 14:16

Publisher DOI:

10.1093/nar/gkx1308

PubMed ID:

29309687

BORIS DOI:

10.7892/boris.108738

URI:

https://boris.unibe.ch/id/eprint/108738

Actions (login required)

Edit item Edit item
Provide Feedback