Translational adaptation to heat stress is mediated by RNA 5-methylcytosine in Caenorhabditis elegans.
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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
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.
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)
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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