Abstract
Methylation of carbon-5 of cytosines (m 5C) is a post-transcriptional nucleotide modification of RNA found in all kingdoms of life. While individual m 5C-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 5C in RNA, demonstrating that this modification is non-essential. Using this genetic tool, we determine the localisation and enzymatic specificity of m 5C 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 5C impacts the decoding of some triplets of these two amino acids, leading to reduced translation efficiency. Upon heat stress, m 5C loss leads to ribosome stalling at UUG triplets, the only codon translated by an m 5C34-modified tRNA. This leads to reduced translation efficiency of UUG-rich transcripts and impaired fertility, suggesting a role of m 5C tRNA wobble methylation in the adaptation to higher temperatures.
Original language | English |
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Article number | e105496 |
Journal | The EMBO Journal |
Volume | 40 |
Issue number | 6 |
Early online date | 7 Dec 2020 |
DOIs | |
Publication status | Published - 15 Mar 2021 |
Keywords
- 5-methylcytosine
- Caenorhabditis elegans
- NSUN
- RNA modifications
- translation efficiency
Profiles
-
Alper Akay
- School of Biological Sciences - UKRI Future Leaders Fellow
- Cells and Tissues - Member
- RNA (epi)Genetics Lab - Group Lead
Person: Group Lead, Research Group Member, Academic, Teaching & Research