RRC ID 65383
Author Navarro IC, Tuorto F, Jordan D, Legrand C, Price J, Braukmann F, Hendrick AG, Akay A, Kotter A, Helm M, Lyko F, Miska EA.
Title Translational adaptation to heat stress is mediated by RNA 5-methylcytosine in Caenorhabditis elegans.
Journal EMBO J
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.
Volume 40(6)
Pages e105496
Published 2021-3-15
DOI 10.15252/embj.2020105496
PMID 33283887
PMC PMC7957426
MeSH 5-Methylcytosine / metabolism* Adaptation, Physiological / genetics* Animals CRISPR-Cas Systems / genetics Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology Cytosine / chemistry Gene Editing Heat-Shock Response / genetics* Hot Temperature Leucine / chemistry Methyltransferases / metabolism Mitochondria / genetics Mitochondria / metabolism Proline / chemistry Protein Biosynthesis / genetics Protein Biosynthesis / physiology RNA / chemistry RNA / genetics RNA Processing, Post-Transcriptional / genetics* Ribosomes / metabolism
C.elegans tm3898