Publications

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

  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., Weinhaeusel A., Mohr T., Steiger M., Mattanovich D., Rinnerthaler M., Karl T., Sharma S., Entian K.D., Kos M., Breitenbach M., Wilson I.B., Polacek N., Grillari-Voglauer R., Breitenbach-Koller L., Grillari J.

  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 th ... >> More

  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. << Less

  Nat. Commun. 6:6158-6158(2015) [PubMed] [EuropePMC]

• The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans.

  Heissenberger C., Rollins J.A., Krammer T.L., Nagelreiter F., Stocker I., Wacheul L., Shpylovyi A., Tav K., Snow S., Grillari J., Rogers A.N., Lafontaine D.L., Schosserer M.

  Our knowledge about the repertoire of ribosomal RNA modifications and the enzymes responsible for installing them is constantly expanding. Previously, we reported that NSUN-5 is responsible for depositing m⁵C at position C2381 on the 26S rRNA in <i>Caenorhabditis elegans</i>. Here, we s ... >> More

  Our knowledge about the repertoire of ribosomal RNA modifications and the enzymes responsible for installing them is constantly expanding. Previously, we reported that NSUN-5 is responsible for depositing m⁵C at position C2381 on the 26S rRNA in <i>Caenorhabditis elegans</i>. Here, we show that NSUN-1 is writing the second known 26S rRNA m⁵C at position C2982. Depletion of <i>nsun-1</i> or <i>nsun-5</i> improved thermotolerance and slightly increased locomotion at midlife, however, only soma-specific knockdown of <i>nsun-1</i> extended lifespan. Moreover, soma-specific knockdown of <i>nsun-1</i> reduced body size and impaired fecundity, suggesting non-cell-autonomous effects. While ribosome biogenesis and global protein synthesis were unaffected by <i>nsun-1</i> depletion, translation of specific mRNAs was remodeled leading to reduced production of collagens, loss of structural integrity of the cuticle, and impaired barrier function. We conclude that loss of a single enzyme required for rRNA methylation has profound and highly specific effects on organismal development and physiology. << Less

  Elife 9:0-0(2020) [PubMed] [EuropePMC]