Translational adaptation to heat stress is mediated by RNA 5-methylcytosine in Caenorhabditis elegans.
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Authors
Jordan, David
Legrand, Carine
Akay, Alper
Kotter, Annika
Helm, Mark
Lyko, Frank
Publication Date
2021-03-15Journal Title
EMBO J
ISSN
0261-4189
Publisher
EMBO
Volume
40
Issue
6
Pages
e105496
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Navarro, I. C., Tuorto, F., Jordan, D., Legrand, C., Price, J., Braukmann, F., Hendrick, A., et al. (2021). Translational adaptation to heat stress is mediated by RNA 5-methylcytosine in Caenorhabditis elegans.. EMBO J, 40 (6), e105496. https://doi.org/10.15252/embj.2020105496
Abstract
Methylation of carbon-5 of cytosines (m5 C) is a post-transcriptional nucleotide modification of RNA found in all kingdoms of life. While individual m5 C-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 m5 C in RNA, demonstrating that this modification is non-essential. Using this genetic tool, we determine the localisation and enzymatic specificity of m5 C 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 m5 C impacts the decoding of some triplets of these two amino acids, leading to reduced translation efficiency. Upon heat stress, m5 C loss leads to ribosome stalling at UUG triplets, the only codon translated by an m5 C34-modified tRNA. This leads to reduced translation efficiency of UUG-rich transcripts and impaired fertility, suggesting a role of m5 C tRNA wobble methylation in the adaptation to higher temperatures.
Sponsorship
Wellcome Trust (104640/Z/14/Z)
Cancer Research UK (A27826)
Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (203144/Z/16/Z)
Cancer Research UK (C6946/A24843)
Identifiers
External DOI: https://doi.org/10.15252/embj.2020105496
This record's URL: https://www.repository.cam.ac.uk/handle/1810/312830
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