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

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
eLife | 2020

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.

Pubmed ID: 33289480

Associated grants

  • Agency: Austrian Science Fund, International
    Id: P30623
  • Agency: Austrian Science Fund, International
    Id: W1224
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: Austrian Science Fund FWF, Austria
    Id: P 30623
  • Agency: Austrian Science Fund, International
    Id: I2514
  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM103423
  • Agency: Austrian Science Fund FWF, Austria
    Id: W 1224
  • Agency: RĂ©gion Wallonne (DGO6), International
    Id: 1810070
  • Agency: Hochschuljubiläumsstiftung der Stadt Wien, International
    Id: H- 327123/2018
  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM104318

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This is a list of tools and resources that we have found mentioned in this publication.


BioCAT (tool)

RRID:SCR_001440

Biomedical technology research center and training resource for the study of the structure of partially ordered biological molecules, complexes of biomolecules and cellular structures under conditions similar to those present in living cells and tissues. The goal of research at BioCAT is to determine the detailed structure and mechanism of action of biological systems at the molecular level. The techniques used are X-ray fiber diffraction, X-ray solution scattering and X-ray micro-emission and micro-absorption spectroscopy, with an emphasis on time-resolved studies and the development of novel techniques.

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DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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RRID:SCR_002037

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RRID:SCR_003098

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RRID:SCR_003210

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RRID:SCR_005622

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RRID:SCR_005677

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RRID:SCR_006151

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RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

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RRID:SCR_008539

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RRID:SCR_008983

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RRID:SCR_014583

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RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

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RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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DCL569 (tool)

RRID:WB-STRAIN:WBStrain00005607

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RRID:AB_2566826

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RRID:SCR_002285

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RRID:SCR_006281

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