期刊
EMBO JOURNAL
卷 40, 期 6, 页码 -出版社
WILEY
DOI: 10.15252/embj.2020105496
关键词
5‐ methylcytosine; Caenorhabditis elegans; NSUN; RNA modifications; translation efficiency
资金
- Wellcome Trust Senior Investigator award [104640/Z/14/Z]
- Cancer Research UK [C13474/A27826, C6946/A24843]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico doctorate scholarship (CNPq, Brazil) [205589/2014-6]
- Deutsche Forschungsgemeinschaft [SPP1784]
- Wellcome Trust [092096/Z/10/Z, 203144/Z/16/Z]
- Wellcome Trust [104640/Z/14/Z, 203144/Z/16/Z] Funding Source: Wellcome Trust
The study demonstrates that m(5)C modification on RNA is non-essential. The localization and enzymatic specificity of m(5)C sites play a key role in rRNA and tRNA methyltransferases. Loss of m(5)C affects the decoding of specific tRNAs, leading to translation efficiency problems.
Methylation of carbon-5 of cytosines (m(5)C) is a post-transcriptional nucleotide modification of RNA found in all kingdoms of life. While individual m(5)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 m(5)C in RNA, demonstrating that this modification is non-essential. Using this genetic tool, we determine the localisation and enzymatic specificity of m(5)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 m(5)C impacts the decoding of some triplets of these two amino acids, leading to reduced translation efficiency. Upon heat stress, m(5)C loss leads to ribosome stalling at UUG triplets, the only codon translated by an m(5)C34-modified tRNA. This leads to reduced translation efficiency of UUG-rich transcripts and impaired fertility, suggesting a role of m(5)C tRNA wobble methylation in the adaptation to higher temperatures.
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