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; Johannes Grillari

doi:10.1038/ncomms7158

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

School of Biology

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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.

Original language	English
Article number	6158
Journal	Nature Communications
Volume	6
Early online date	30 Jan 2015
DOIs	https://doi.org/10.1038/ncomms7158
Publication status	Published - 2015

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Schosserer, M., Minois, N., Angerer, T. B., Amring, M., Dellago, H., Harreither, E., Calle-Perez, A., Pircher, A., Gerstl, M. P., Pfeifenberger, S., Brandl, C., Sonntagbauer, M., Kriegner, A., Linder, A., Weinhäusel, A., Mohr, T., Steiger, M., Mattanovich, D., Rinnerthaler, M., ... Grillari, J. (2015). Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan. Nature Communications, 6, Article 6158. https://doi.org/10.1038/ncomms7158

@article{6243ea3ce8d94a469b494fbdf2ca4e96,

title = "Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan",

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.",

author = "Markus Schosserer and Nadege Minois and Angerer, {Tina B} and Manuela Amring and Hanna Dellago and Eva Harreither and Alfonso Calle-Perez and Andreas Pircher and Gerstl, {Matthias Peter} and Sigrid Pfeifenberger and Clemens Brandl and Markus Sonntagbauer and Albert Kriegner and Angela Linder and Andreas Weinh{\"a}usel and Thomas Mohr and Matthias Steiger and Diethard Mattanovich and Mark Rinnerthaler and Thomas Karl and Sunny Sharma and Karl-Dieter Entian and Martin Kos and Michael Breitenbach and Wilson, {Iain B H} and Norbert Polacek and Regina Grillari-Voglauer and Lore Breitenbach-Koller and Johannes Grillari",

year = "2015",

doi = "10.1038/ncomms7158",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature publishing group",

}

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, K-D, Kos, M, Breitenbach, M, Wilson, IBH, Polacek, N, Grillari-Voglauer, R, Breitenbach-Koller, L & Grillari, J 2015, 'Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan', Nature Communications, vol. 6, 6158. https://doi.org/10.1038/ncomms7158

TY - JOUR

T1 - Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan

AU - Schosserer, Markus

AU - Minois, Nadege

AU - Angerer, Tina B

AU - Amring, Manuela

AU - Dellago, Hanna

AU - Harreither, Eva

AU - Calle-Perez, Alfonso

AU - Pircher, Andreas

AU - Gerstl, Matthias Peter

AU - Pfeifenberger, Sigrid

AU - Brandl, Clemens

AU - Sonntagbauer, Markus

AU - Kriegner, Albert

AU - Linder, Angela

AU - Weinhäusel, Andreas

AU - Mohr, Thomas

AU - Steiger, Matthias

AU - Mattanovich, Diethard

AU - Rinnerthaler, Mark

AU - Karl, Thomas

AU - Sharma, Sunny

AU - Entian, Karl-Dieter

AU - Kos, Martin

AU - Breitenbach, Michael

AU - Wilson, Iain B H

AU - Polacek, Norbert

AU - Grillari-Voglauer, Regina

AU - Breitenbach-Koller, Lore

AU - Grillari, Johannes

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.nature.com/ncomms/2015/150130/ncomms7158/full/ncomms7158.html#supplementary-information

U2 - 10.1038/ncomms7158

DO - 10.1038/ncomms7158

M3 - Article

C2 - 25635753

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 6158

ER -

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

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