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

Markus Schosserer, Nadege Minois, Tina B. Angerer, Manuela Amring, Hanna Dellago, Eva Harreither, Alfonso Calle-Perez, Andreas Pircher, Matthias Peter Gerstl, Sigrid Pfeifenberger, Clemens Brandl, Markus Sonntagbauer, Albert Kriegner, Angela Linder, Andreas Weinhäusel, Thomas Mohr, Matthias Steiger, Diethard Mattanovich, Mark Rinnerthaler, Thomas Karl, Sunny Sharma, Karl-Dieter Entian, Martin Kos, Michael Breitenbach, Iain B.H. Wilson, Norbert Polacek, Regina Grillari-Voglauer, Lore Breitenbach-Koller () and Johannes Grillari ()
Additional contact information
Markus Schosserer: BOKU—University of Natural Resources and Life Sciences, Vienna
Nadege Minois: Biomedical Sciences Research Complex, University of St Andrews
Tina B. Angerer: University of Salzburg
Manuela Amring: University of Salzburg
Hanna Dellago: BOKU—University of Natural Resources and Life Sciences, Vienna
Eva Harreither: BOKU—University of Natural Resources and Life Sciences, Vienna
Alfonso Calle-Perez: BOKU—University of Natural Resources and Life Sciences, Vienna
Andreas Pircher: University of Bern
Matthias Peter Gerstl: ACIB GmbH–Austrian Centre of Industrial Biotechnology
Sigrid Pfeifenberger: University of Salzburg
Clemens Brandl: University of Salzburg
Markus Sonntagbauer: Molecular Medicine, AIT Austrian Institute of Technology GmbH
Albert Kriegner: Molecular Medicine, AIT Austrian Institute of Technology GmbH
Angela Linder: BOKU—University of Natural Resources and Life Sciences, Vienna
Andreas Weinhäusel: Molecular Medicine, AIT Austrian Institute of Technology GmbH
Thomas Mohr: Science Consult DI Thomas Mohr KG
Matthias Steiger: BOKU—University of Natural Resources and Life Sciences, Vienna
Diethard Mattanovich: BOKU—University of Natural Resources and Life Sciences, Vienna
Mark Rinnerthaler: University of Salzburg
Thomas Karl: University of Salzburg
Sunny Sharma: Institute of Molecular Biosciences, Goethe University
Karl-Dieter Entian: Institute of Molecular Biosciences, Goethe University
Martin Kos: Biochemie-Zentrum der Universität Heidelberg (BZH)
Michael Breitenbach: University of Salzburg
Iain B.H. Wilson: BOKU—University of Natural Resources and Life Sciences, Vienna
Norbert Polacek: University of Bern
Regina Grillari-Voglauer: BOKU—University of Natural Resources and Life Sciences, Vienna
Lore Breitenbach-Koller: University of Salzburg
Johannes Grillari: BOKU—University of Natural Resources and Life Sciences, Vienna

Nature Communications, 2015, vol. 6, issue 1, 1-17

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms7158

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