The ribosomal RNA m⁵C methyltransferase NSUN-1 modulates healthspan and oogenesis in <i>Caenorhabditis elegans</i>.

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.