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

• Main Authors: Clemens Heissenberger, Jarod A Rollins, Teresa L Krammer, Fabian Nagelreiter, Isabella Stocker, Ludivine Wacheul, Anton Shpylovyi, Koray Tav, Santina Snow, Johannes Grillari, Aric N Rogers, Denis L J Lafontaine, Markus Schosserer
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2020-12-01
• Series: eLife
• Subjects: aging; RNA methylation; ribosome; translation; nsun1/nop2/p120; nsun5/rcm1
• Online Access: https://elifesciences.org/articles/56205

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 thermotolerance and slightly increased locomotion at midlife, 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 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.