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

Elife. 2020 Dec 8:9:e56205. doi: 10.7554/eLife.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.

Keywords: C. elegans; RNA methylation; aging; cell biology; developmental biology; nsun1/nop2/p120; nsun5/rcm1; ribosome; translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / metabolism*
  • Female
  • Fertility / physiology
  • Longevity / physiology*
  • Methyltransferases / metabolism*
  • Oogenesis / physiology
  • RNA Processing, Post-Transcriptional / physiology


  • Caenorhabditis elegans Proteins
  • Methyltransferases
  • m(5)C rRNA methyltransferase

Associated data

  • GEO/GSE143618