The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis inCaenorhabditis 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 m 5 C at position C2381 on the 26S rRNA in Caenorhabditis elegans . Here, we show that NSUN-1 is writing the second known 26S rRNA m 5 C 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.