Schosserer, M. | Search bioRxiv

bioRxiv2020

Cellular senescence and quiescence are associated with altered ribosomal RNA methylation and processing

The 2-O-methylation (2-O-Me) of ribosomal RNA (rRNA) shows plasticity potentially associated with specific cell phenotypes. We used RiboMeth-seq profiling to reveal 2-O-Me patterns specific to stress induced premature senescent (SIPS), quiescent and proliferating human dermal fibroblasts. The altered methylation levels in SIPS and quiescence partially correlated with the expression of specific snoRNAs but not fibrillarin. Senescence and quiescence were accompanied by a trend towards preferred usage of one of the two alternative ribosome biogenesis pathways.

molecular biology↗

bioRxiv2020

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

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 Caenorhabditis elegans. Here, we show that NSUN-1 is writing the second known 26S rRNA m5C at position C2982. Depletion of nsun-1 or nsun-5 improved locomotion at midlife and resistance against heat stress, however, only soma-specific knockdown of nsun-1 extended lifespan. Moreover, soma-specific knockdown of nsun-1 reduced body size and impaired fecundity, suggesting non-cell-autonomous effects. While ribosome biogenesis and global protein synthesis were unaffected by nsun-1 depletion, translation of specific mRNAs was remodelled 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 physiology.

cell biology↗