Schosserer Markus, Minois Nadege, Angerer Tina B, Amring Manuela, Dellago Hanna, Harreither Eva, Calle-Perez Alfonso, Pircher Andreas, Gerstl Matthias Peter, Pfeifenberger Sigrid, Brandl Clemens, Sonntagbauer Markus, Kriegner Albert, Linder Angela, Weinhäusel Andreas, Mohr Thomas, Steiger Matthias, Mattanovich Diethard, Rinnerthaler Mark, Karl Thomas, Sharma Sunny, Entian Karl-Dieter, Kos Martin, Breitenbach Michael, Wilson Iain B H, Polacek Norbert, Grillari-Voglauer Regina, Breitenbach-Koller Lore, Grillari Johannes
Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria.
Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
Nat Commun. 2015 Jan 30;6:6158. doi: 10.1038/ncomms7158.
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.
几种调节寿命和抗逆性的途径通过靶向核糖体蛋白或起始因子汇聚于翻译过程，但这是否涉及核糖体RNA的修饰尚不清楚。在这里，我们表明保守的RNA甲基转移酶NSUN5水平降低会延长酵母、线虫和果蝇的寿命并增强其抗逆性。NSUN5的酵母同源物Rcm1可使25S rRNA保守区域内的C2278甲基化。Rcm1的缺失会改变核糖体靠近C2278处的结构构象以及翻译保真度，并有利于将一组不同的氧化应激反应性mRNA招募到多核糖体中。因此，核糖体并非仅仅是执行翻译的静态分子机器，而是通过仅修饰单个rRNA核苷酸就展现出功能多样性，从而导致生物体生理行为的改变，并将rRNA介导的翻译调控与寿命调节和不同的应激反应联系起来。
