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

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.

SUBMITTER: Navarro IC 

PROVIDER: S-EPMC7957426 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature