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Gewählte Doctoral Thesis:

Guohuan Yang (2020): The role of 2’-O-methylation of ribosomal RNA in aging and stress resistance.
Doctoral Thesis - Institut für Bioverfahrenstechnik, BOKU-Universität für Bodenkultur, pp 196. UB BOKU obvsg FullText

Abstract:

The role of 2’-O-Me in ribosome biogenesis and ribosome function is believed to be important, but how 2’-O-Me participates in those processes remains unclear. We found that cellular senescence is accompanied by a preferred usage of one of the two alternative ribosome biogenesis pathways. Using RiboMeth-seq profiling, we identified an altered methylation pattern in senescent vs. proliferating or quiescent human dermal fibroblasts, thus providing the first repertoire of 2’-O-Me sites usage in cellular senescence, supporting the “specialized ribosome” hypothesis. Our study indicated that the modification level of most of the senescence- and quiescence-specific 2’-O-Mes were correlated with the expression of their specific snoRNAs but not fibrillarin. Intriguingly, knockdown of the specific snoRNAs guiding altered methylation sites in human dermal fibroblasts suggested a link with proliferation capability and cell death. Loss of modifications at residues in rRNA has the potential to play a vital role in chronological lifespan (CLS) in Saccharomyces cerevisiae. Therefore, we examined the CLS and stress resistance of yeast in response to the deletion of single and multiple rRNA modifications. Our results suggest that rRNA modifications modulate yeast’s cellular fitness in a structural-specific manner indicated by sensitivity changes in response to specific stressors. Promisingly, strain snr65Δ, lacking an individual 2’-O-Me at nucleotide U2347 in the vicinity to the polypeptide exit tunnel, showed slightly growth superiority. However, blocking most modification sites had no evident beneficial impact on CLS. Nevertheless, strain snr41Δsnr51Δsnr70Δ with five modifications absent in the small subunit, and snr60Δ with two methylations absent close to the peptidyl transferase center, displayed impaired CLS. Overall, rRNA modifications variation shows a minor impact on CLS, while a small number of them might play a potential role in CLS adjustment.

Betreuer: Grillari Johannes

1. Berater: Schosserer Markus