Translational adaptation to heat stress is mediated by RNA 5‐methylcytosine in Caenorhabditis elegans

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Cunha Navarro, Isabela, Tuorto, Francesca, Jordan, David, Legrand, Carine, Price, Jonathan, Braukmann, Fabian, Hendrick, Alan G., Akay, Alper, 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:	http://www.scopus.com/inward/record.url?... https://www.embopress.org/doi/full/10.15...
Depositing User:	LivePure Connector
Date Deposited:	09 Dec 2020 01:07
Last Modified:	31 Jan 2025 01:05
URI:	https://ueaeprints.uea.ac.uk/id/eprint/77917
DOI:

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