RRC ID 32381
Author Schosserer M, Minois N, Angerer TB, Amring M, Dellago H, Harreither E, Calle-Perez A, Pircher A, Gerstl MP, Pfeifenberger S, Brandl C, Sonntagbauer M, Kriegner A, Linder A, Weinhäusel A, Mohr T, Steiger M, Mattanovich D, Rinnerthaler M, Karl T, Sharma S, Entian KD, Kos M, Breitenbach M, Wilson IB, Polacek N, Grillari-Voglauer R, Breitenbach-Koller L, Grillari J.
Title Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan.
Journal Nat Commun
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.
Volume 6
Pages 6158
Published 2015-1-30
DOI 10.1038/ncomms7158
PII ncomms7158
PMID 25635753
PMC PMC4317494
MeSH Animals Drosophila Female Hermaphroditic Organisms / genetics Hermaphroditic Organisms / physiology Humans Life Expectancy Male Methylation* Mice RNA, Ribosomal / genetics* RNA, Ribosomal / physiology Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae / physiology
IF 12.353
Times Cited 28
C.elegans tm3898
Drosophila dNsun5