The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans
- University of Natural Resources and Life Sciences, Vienna, Austria
- MDI Biological Laboratory, United States
- Université Libre de Bruxelles, Belgium
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 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.
Data availability
The raw and processed sequencing data are available from the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo) under accession GSE143618. Analyzed RNA-seq data are provided as Supplemental Data File 1-4. The R-script for analyzing RNA-seq data is provided as Supplemental Data File 5. Statistics for individual replicates of lifespan and stress-resistance experiments are reported in Table 1. Raw data of lifespan and thermotolerance assays are provided as Figure 2-source data 1.
Article and author information
Author details
Denis LJ Lafontaine
Funding
Austrian Science Fund (P30623)
- Markus Schosserer
Herzfelder'sche Familienstiftung (P30623)
- Markus Schosserer
Hochschuljubiläumsstiftung der Stadt Wien (H- 327123/2018)
- Markus Schosserer
Austrian Science Fund (I2514,W1224)
- Johannes Grillari
National Institute of General Medical Sciences (P20GM103423,P20GM104318)
- Jarod A Rollins
- Aric N Rogers
Fonds De La Recherche Scientifique - FNRS
- Denis LJ Lafontaine
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Heissenberger et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans
eLife 9:e56205.
https://doi.org/10.7554/eLife.56205
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