Nsun5 in ribosome function and mammalian healthy lifespan
Abstract
We found previously that lack of a specific m5C methylation on 28S ribosomal RNA conferred by Nsun5 leads to increased lifespan and stress resistance of yeast, worms and flies. However, if Nsun5 or any other RNA methyltransferase is also capable of modulating healthy lifespan of mammals is not known. Thus, the aims of this project encompass the measurement of the lifespan of a Nsun5 constitutive whole-body knockout mouse model compared to littermate controls, as well as phenotypic evaluation of health that we hypothesize to be improved by Nsun5 knockout at advanced age. Mice of both sexes in a C57BL6/J background will be tested. We further hypothesize that loss of Nsun5 also increases stress resistance on cellular level and alters ribosome function. This hypothesis will be tested by characterization of Nsun5 activity in different tissues and at different timepoints during the lifespan, assessment of cellular fitness by measurement of stress resistance in-vitro, as well as translation rate and fidelity. We will further isolate mRNAs contained in ribosomes by immunoprecipitation utilizing the ribo-tag platform, and compare their expression to total cellular mRNAs. Thereby we will be able to identify global gene expression patterns of translational regulation and confirm the presence of similar regulatory elements as we found in yeast, such as upstream open reading frames. Due to the high evolutionary conservation of Nsun5, we are convinced that conclusions obtained within this project are also applicable to humans. Thus, the experiments proposed here will contribute to a better understanding of the contribution of ribosomal RNA methylation to organismal fitness and probably pave the ground for the design of healthspan extending strategies in humans.
keywords RNA methylation aging research mouse models frailty healthspan
Publikationen
Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases.
Autoren: Cardoso, AL; Fernandes, A; Aguilar-Pimentel, JA; de Angelis, MH; Guedes, JR; Brito, MA; Ortolano, S; Pani, G; Athanasopoulou, S; Gonos, ES; Schosserer, M; Grillari, J; Peterson, P; Tuna, BG; Dogan, S; Meyer, A; van Os, R; Trendelenburg, AU; Jahr: 2018
Journal articles
Modelling physical resilience in ageing mice.
Autoren: Schosserer, M; Banks, G; Dogan, S; Dungel, P; Fernandes, A; Marolt Presen, D; Matheu, A; Osuchowski, M; Potter, P; Sanfeliu, C; Tuna, BG; Varela-Nieto, I; Bellantuono, I; Jahr: 2019
Journal articles
Raman fingerprints as promising markers of cellular senescence and aging.
Autoren: Liendl, L; Grillari, J; Schosserer, M; Jahr: 2020
Journal articles
Specialized ribosomes in human dermal fibroblast senescence
Autoren: Nagelreiter, F; Yang, G; Heissenberger, C; Gonskikh, Y; Polacek, N; Grillari, J; Kos, M; Schosserer, M Jahr: 2019
Journal articles
Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth.
Autoren: Heissenberger, C; Liendl, L; Nagelreiter, F; Gonskikh, Y; Yang, G; Stelzer, EM; Krammer, TL; Micutkova, L; Vogt, S; Kreil, DP; Sekot, G; Siena, E; Poser, I; Harreither, E; Linder, A; Ehret, V; Helbich, TH; Grillari-Voglauer, R; Jansen-Dürr, P; Koš, M; Polacek, N; Grillari, J; Schosserer, M; Jahr: 2019
Journal articles
Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated by N-glycans but by heparan sulfate proteoglycan interactions.
Autoren: Gludovacz, E; Schuetzenberger, K; Resch, M; Tillmann, K; Petroczi, K; Vondra, S; Vakal, S; Schosserer, M; Virgolini, N; Pollheimer, J; Salminen, TA; Jilma, B; Borth, N; Boehm, T; Jahr: 2021
Journal articles
Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory Study.
Autoren: Guo, S; Beleites, C; Neugebauer, U; Abalde-Cela, S; Afseth, NK; Alsamad, F; Anand, S; Araujo-Andrade, C; Aškrabić, S; Avci, E; Baia, M; Baranska, M; Baria, E; Batista de Carvalho, LAE; de Bettignies, P; Bonifacio, A; Bonnier, F; Brauchle, EM; Byrne, HJ; Chourpa, I; Cicchi, R; Cuisinier, F; Culha, M; Dahms, M; David, C; Duponchel, L; Duraipandian, S; El-Mashtoly, SF; Ellis, DI; Eppe, G; Falgayrac, G; Gamulin, O; Gardner, B; Gardner, P; Gerwert, K; Giamarellos-Bourboulis, EJ; Gizurarson, S; Gnyba, M; Goodacre, R; Grysan, P; Guntinas-Lichius, O; Helgadottir, H; Grošev, VM; Kendall, C; Kiselev, R; Kölbach, M; Krafft, C; Krishnamoorthy, S; Kubryck, P; Lendl, B; Loza-Alvarez, P; Lyng, FM; Machill, S; Malherbe, C; Marro, M; Marques, MPM; Matuszyk, E; Morasso, CF; Moreau, M; Muhamadali, H; Mussi, V; Notingher, I; Pacia, MZ; Pavone, FS; Penel, G; Petersen, D; Piot, O; Rau, JV; Richter, M; Rybarczyk, MK; Salehi, H; Schenke-Layland, K; Schlücker, S; Schosserer, M; Schütze, K; Sergo, V; Sinjab, F; Smulko, J; Sockalingum, GD; Stiebing, C; Stone, N; Untereiner, V; Vanna, R; Wieland, K; Popp, J; Bocklitz, T; Jahr: 2020
Journal articles
Targeting cellular senescence based on interorganelle communication, multilevel proteostasis, and metabolic control.
Autoren: Cavinato, M; Madreiter-Sokolowski, CT; Büttner, S; Schosserer, M; Zwerschke, W; Wedel, S; Grillari, J; Graier, WF; Jansen-Dürr, P; Jahr: 2021
Journal articles
The ribosomal RNA m 5 C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans
Autoren: Heissenberger, C; Rollins, JA; Krammer, TL; Nagelreiter, F; Stocker, I; Wacheul, L; Shpylovyi, A; Tav, K; Snow, S; Grillari, J; Rogers, AN; Lafontaine, DLJ; Schosserer, M; Jahr: 2020
Journal articles
Project staff
Markus Schosserer
Dipl.-Ing. Dr. Markus Schosserer
markus.schosserer@boku.ac.at
Tel: +43 1 47654-79067
Project Leader
01.05.2018 - 31.12.2021
Lisa Liendl
Mag. Lisa Liendl
Tel: +43 1 47654-79048, 79050, 79057
Project Staff
01.06.2018 - 30.04.2021