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bioRxiv · 10.1101/2020.03.16.993469

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

Heissenberger, C.·Krammer, T. L.·Rollins, J. A.·Nagelreiter, F.·Stocker, I.·Wacheul, L.·Shpylovyi, A.·Snow, S.·Grillari, J.·Rogers, A.·Lafontaine, D. L.·Schosserer, M.
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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 locomotion at midlife and resistance against heat stress, 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 remodelled 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 physiology.

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Heissenberger, C., Krammer, T. L., Rollins, J. A., Nagelreiter, F., Stocker, I., Wacheul, L., Shpylovyi, A., Snow, S., Grillari, J., Rogers, A., Lafontaine, D. L., Schosserer, M.. 2020-03-18. The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans. https://doi.org/10.1101/2020.03.16.993469

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