Translational adaptation to heat stress is mediated by 5-methylcytosine RNA modification inCaenorhabditis elegans

Abstract

ABSTRACTMethylation of carbon-5 of cytosines (m5C) is a post-transcriptional nucleotide modification of RNA found in all kingdoms of life. While individual m5C-methyltransferases have been studied, the impact of the global cytosine-5 methylome on development, homeostasis and stress remains unknown. Here, usingCaenorhabditis elegans, we generated the first organism devoid of m5C in RNA, demonstrating that this modification is non-essential. We determined the localisation and enzymatic specificity of m5C sites in RNAin vivoand showed that animals devoid of m5C are sensitive to temperature stress. At the molecular level, we showed that loss of m5C specifically impacts decoding of leucine and proline thus reducing the translation efficiency of transcripts enriched in these amino acids. Finally, we found translation of leucine UUG codons to be the most strongly affected upon heat shock, suggesting a role of m5C tRNA wobble methylation in the adaptation to heat stress.