Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan

Schosserer, Markus; Minois, Nadege; Angerer, Tina B.; Amring, Manuela; Dellago, Hanna; Harreither, Eva; Calle-Perez, Alfonso; Pircher, Andreas; Gerstl, Matthias Peter; Pfeifenberger, Sigrid; Brandl, Clemens; Sonntagbauer, Markus; Kriegner, Albert; Linder, Angela; Weinhäusel, Andreas; Mohr, Thomas; Steiger, Matthias; Mattanovich, Diethard; Rinnerthaler, Mark; Karl, Thomas; ... (2015). Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan. Nature communications, 6(6158), p. 6158. Nature Publishing Group 10.1038/ncomms7158

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Several pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is unclear. Here, we show that reduced levels of the conserved RNA methyltransferase NSUN5 increase the lifespan and stress resistance in yeast, worms and flies. Rcm1, the yeast homologue of NSUN5, methylates C2278 within a conserved region of 25S rRNA. Loss of Rcm1 alters the structural conformation of the ribosome in close proximity to C2278, as well as translational fidelity, and favours recruitment of a distinct subset of oxidative stress-responsive mRNAs into polysomes. Thus, rather than merely being a static molecular machine executing translation, the ribosome exhibits functional diversity by modification of just a single rRNA nucleotide, resulting in an alteration of organismal physiological behaviour, and linking rRNA-mediated translational regulation to modulation of lifespan, and differential stress response.

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:

Pircher, Andreas and Polacek, Norbert

Subjects:

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

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Christina Schüpbach

Date Deposited:

26 Feb 2015 15:52

Last Modified:

10 Sep 2017 12:56

Publisher DOI:

10.1038/ncomms7158

BORIS DOI:

10.7892/boris.63526

URI:

https://boris.unibe.ch/id/eprint/63526

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