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

Abstract

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.