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.
authors: Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria.
authors: Markus
authors: M
authors: Schosserer
authors: Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
authors: Nadege
authors: N
authors: Minois
authors: Department of Cell Biology, Division of Genetics, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors: Tina B
authors: TB
authors: Angerer
authors: Department of Cell Biology, Division of Genetics, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors: Manuela
authors: M
authors: Amring
authors: 1] Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria [2] Christian Doppler Laboratory on Biotechnology of Skin Aging, Muthgasse 18, 1190 Vienna, Austria.
authors: Hanna
authors: H
authors: Dellago
authors: Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria.
authors: Eva
authors: E
authors: Harreither
authors: Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria.
authors: Alfonso
authors: A
authors: Calle-Perez
authors: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
authors: Andreas
authors: A
authors: Pircher
authors: ACIB GmbH-Austrian Centre of Industrial Biotechnology, Muthgasse 11, 1190 Vienna, Austria.
authors: Matthias Peter
authors: MP
authors: Gerstl
authors: Department of Cell Biology, Division of Genetics, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors: Sigrid
authors: S
authors: Pfeifenberger
authors: Department of Cell Biology, Division of Genetics, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors: Clemens
authors: C
authors: Brandl
authors: Health &Environment Department, Molecular Medicine, AIT Austrian Institute of Technology GmbH, Muthgasse 11, 1190 Vienna, Austria.
authors: Markus
authors: M
authors: Sonntagbauer
authors: Health &Environment Department, Molecular Medicine, AIT Austrian Institute of Technology GmbH, Muthgasse 11, 1190 Vienna, Austria.
authors: Albert
authors: A
authors: Kriegner
authors: Department of Chemistry, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria.
authors: Angela
authors: A
authors: Linder
authors: Health &Environment Department, Molecular Medicine, AIT Austrian Institute of Technology GmbH, Muthgasse 11, 1190 Vienna, Austria.
authors: Andreas
authors: A
authors: Weinhäusel
authors: Science Consult DI Thomas Mohr KG, Enzianweg 10a, 2353 Guntramsdorf, Austria.
authors: Thomas
authors: T
authors: Mohr
authors: 1] Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria [2] ACIB GmbH-Austrian Centre of Industrial Biotechnology, Muthgasse 11, 1190 Vienna, Austria.
authors: Matthias
authors: M
authors: Steiger
authors: 1] Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria [2] ACIB GmbH-Austrian Centre of Industrial Biotechnology, Muthgasse 11, 1190 Vienna, Austria.
authors: Diethard
authors: D
authors: Mattanovich
authors: Department of Cell Biology, Division of Genetics, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors: Mark
authors: M
authors: Rinnerthaler
authors: Department of Cell Biology, Division of Genetics, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors: Thomas
authors: T
authors: Karl
authors: Department of Molecular Genetics &Cellular Microbiology, Institute of Molecular Biosciences, Goethe University, Max-von-Laue-Strasse 9, 60438 Frankfurt/M, Germany.
authors: Sunny
authors: S
authors: Sharma
authors: Department of Molecular Genetics &Cellular Microbiology, Institute of Molecular Biosciences, Goethe University, Max-von-Laue-Strasse 9, 60438 Frankfurt/M, Germany.
authors: Karl-Dieter
authors: KD
authors: Entian
authors: Biochemie-Zentrum der Universität Heidelberg (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
authors: Martin
authors: M
authors: Kos
authors: Department of Cell Biology, Division of Genetics, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors: Michael
authors: M
authors: Breitenbach
authors: Department of Chemistry, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria.
authors: Iain B H
authors: IB
authors: Wilson
authors: Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
authors: Norbert
authors: N
authors: Polacek
authors: 1] Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria [2] ACIB GmbH-Austrian Centre of Industrial Biotechnology, Muthgasse 11, 1190 Vienna, Austria [3] Evercyte GmbH, Muthgasse 18, 1190 Vienna, Austria.
authors: Regina
authors: R
authors: Grillari-Voglauer
authors: Department of Cell Biology, Division of Genetics, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria.
authors: Lore
authors: L
authors: Breitenbach-Koller
authors: 1] Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria [2] Christian Doppler Laboratory on Biotechnology of Skin Aging, Muthgasse 18, 1190 Vienna, Austria [3] ACIB GmbH-Austrian Centre of Industrial Biotechnology, Muthgasse 11, 1190 Vienna, Austria [4] Evercyte GmbH, Muthgasse 18, 1190 Vienna, Austria.
authors: Johannes
authors: J
authors: Grillari
mesh_terms: D000818:Animals; D004330:Drosophila; D005260:Female; D057850:Hermaphroditic Organisms / Q000235:genetics / Q000502:physiology; D006801:Humans; D008017:Life Expectancy; D008297:Male; D008745:Methylation; D051379:Mice; D012335:RNA, Ribosomal / Q000235:genetics* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology
chemical_list: D012335:RNA, Ribosomal
references: Curr Biol. 2004 May 25;14(10):885-90
references: 15186745
references: Aging Cell. 2010 Dec;9(6):1084-97
references: 20883526
references: RNA. 2014 Oct;20(10):1632-44
references: 25125595
references: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references: 16199517
references: Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17394-9
references: 23045643
references: Nat Cell Biol. 2009 Nov;11(11):1305-14
references: 19801973
references: Cell. 2009 Oct 2;139(1):149-60
references: 19804760
references: Mol Syst Biol. 2008;4:180
references: 18414481
references: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10096-101
references: 11517305
references: PLoS Genet. 2007 Apr 6;3(4):e56
references: 17411345
references: Exp Gerontol. 2006 Dec;41(12):1208-12
references: 17126512
references: Mol Biol Cell. 2012 Nov;23(21):4313-22
references: 22956767
references: Genetics. 2003 Jan;163(1):35-46
references: 12586694
references: Nature. 2003 Oct 16;425(6959):686-91
references: 14562095
references: Genetics. 1974 May;77(1):71-94
references: 4366476
references: Science. 2005 Nov 18;310(5751):1193-6
references: 16293764
references: Cell Metab. 2010 Sep 8;12(3):260-72
references: 20816092
references: PLoS One. 2013;8(7):e67609
references: 23861776
references: Cytogenet Cell Genet. 2001;95(1-2):20-7
references: 11978965
references: PLoS Genet. 2005 Jul;1(1):119-28
references: 16103914
references: RNA. 2000 Aug;6(8):1174-84
references: 10943896
references: Aging Cell. 2007 Feb;6(1):111-9
references: 17266680
references: Nat Rev Mol Cell Biol. 2012 Jun;13(6):355-69
references: 22617470
references: Nat Biotechnol. 2013 May;31(5):458-64
references: 23604283
references: Cell Metab. 2011 Jul 6;14(1):55-66
references: 21723504
references: J Vis Exp. 2010;(40). pii: 1948. doi: 10.3791/1948
references: 20567211
references: RNA. 1998 Oct;4(10):1282-94
references: 9769102
references: J Biol Chem. 2006 Sep 29;281(39):29011-21
references: 16849329
references: Nucleic Acids Res. 2009 Feb;37(2):e12
references: 19059995
references: Nucleic Acids Res. 1999 Jan 1;27(1):196-7
references: 9847178
references: Stat Appl Genet Mol Biol. 2004;3:Article3
references: 16646809
references: Biochemistry. 2002 Sep 17;41(37):11218-25
references: 12220187
references: Genes Dev. 2006 Jan 15;20(2):174-84
references: 16418483
references: Cell. 2008 Apr 18;133(2):292-302
references: 18423200
references: Adv Exp Med Biol. 2010;694:30-7
references: 20886754
references: Nature. 2007 Feb 22;445(7130):922-6
references: 17277769
references: Nat Commun. 2012;3:937
references: 22760636
references: Science. 2009 Oct 2;326(5949):140-4
references: 19797661
references: Aging (Albany NY). 2012 Apr;4(4):290-304
references: 22529335
references: FEBS Lett. 2013 Apr 17;587(8):1189-97
references: 23485824
references: Gene. 2001 Jan 24;263(1-2):103-12
references: 11223248
references: Exp Gerontol. 2007 Apr;42(4):275-86
references: 17174052
references: Aging (Albany NY). 2009 Jul;1(7):622-36
references: 20157544
references: Nature. 1993 Dec 2;366(6454):461-4
references: 8247153
references: Aging Cell. 2007 Feb;6(1):95-110
references: 17266679
references: J Mol Biol. 1970 Mar;48(3):443-53
references: 5420325
references: Cold Spring Harb Protoc. 2010 Oct;2010(10):pdb.prot5505
references: 20889702
references: BMC Genomics. 2009;10:7
references: 19128476
references: Nature. 2007 Jul 12;448(7150):151-6
references: 17625558
references: Nucleic Acids Res. 2013 Oct;41(19):9062-76
references: 23913415
references: Can J Microbiol. 1997 Aug;43(8):774-81
references: 9304788
references: Aging Cell. 2010 Aug;9(4):490-505
references: 20497132