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 KarlSunny Sharma, Karl-Dieter Entian, Martin Kos, Michael Breitenbach, Iain B H Wilson, Norbert Polacek, Regina Grillari-Voglauer, Lore Breitenbach-Koller, Johannes Grillari

Research output: Contribution to journalArticlepeer-review

122 Citations (Scopus)


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.
Original languageEnglish
Article number6158
JournalNature Communications
Early online date30 Jan 2015
Publication statusPublished - 2015


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