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Cunha Navarro, Isabela, Tuorto, Francesca, Jordan, David, Legrand, Carine, Price, Jonathan, Braukmann, Fabian, Hendrick, Alan G., Akay, Alper 
ORCID: https://orcid.org/0000-0001-6825-4443, Kotter, Annika, Helm, Mark, Lyko, Frank and Miska, Eric A.
(2021)
Translational adaptation to heat stress is mediated by RNA 5‐methylcytosine in Caenorhabditis elegans.
The EMBO Journal, 40 (6).
ISSN 0261-4189
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Abstract
Methylation of carbon-5 of cytosines (m 5C) is a post-transcriptional nucleotide modification of RNA found in all kingdoms of life. While individual m 5C-methyltransferases have been studied, the impact of the global cytosine-5 methylome on development, homeostasis and stress remains unknown. Here, using Caenorhabditis elegans, we generated the first organism devoid of m 5C in RNA, demonstrating that this modification is non-essential. Using this genetic tool, we determine the localisation and enzymatic specificity of m 5C sites in the RNome in vivo. We find that NSUN-4 acts as a dual rRNA and tRNA methyltransferase in C. elegans mitochondria. In agreement with leucine and proline being the most frequently methylated tRNA isoacceptors, loss of m 5C impacts the decoding of some triplets of these two amino acids, leading to reduced translation efficiency. Upon heat stress, m 5C loss leads to ribosome stalling at UUG triplets, the only codon translated by an m 5C34-modified tRNA. This leads to reduced translation efficiency of UUG-rich transcripts and impaired fertility, suggesting a role of m 5C tRNA wobble methylation in the adaptation to higher temperatures.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 5-methylcytosine,caenorhabditis elegans,nsun,rna modifications,translation efficiency,neuroscience(all),molecular biology,biochemistry, genetics and molecular biology(all),immunology and microbiology(all) ,/dk/atira/pure/subjectarea/asjc/2800 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 09 Dec 2020 01:07 |
| Last Modified: | 20 Apr 2023 19:34 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/77917 |
| DOI: | 10.15252/embj.2020105496 |
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