2020
Navarro, Isabela Cunha; Tuorto, Francesca; Jordan, David; Legrand, Carine; Price, Jonathan; Braukmann, Fabian; Hendrick, Alan G.; Akay, Alper; Kotter, Annika; Helm, Mark; Lyko, Frank; Miska, Eric A.
Translational adaptation to heat stress is mediated by RNA 5‐methylcytosine in Caenorhabditis elegans Journal Article
In: The EMBO Journal, vol. 40, no. 6, pp. EMBJ2020105496, 2020, ISSN: 1460-2075.
Abstract | Links | BibTeX | Tags: 5‐methylcytosine, Caenorhabditis elegans, NSUN, RNA modifications, translation efficiency
@article{navarro_translational_2020,
title = {Translational adaptation to heat stress is mediated by RNA 5‐methylcytosine in Caenorhabditis elegans},
author = {Isabela Cunha Navarro and Francesca Tuorto and David Jordan and Carine Legrand and Jonathan Price and Fabian Braukmann and Alan G. Hendrick and Alper Akay and Annika Kotter and Mark Helm and Frank Lyko and Eric A. Miska},
url = {https://doi.org/10.15252/embj.2020105496},
doi = {10.15252/embj.2020105496},
issn = {1460-2075},
year = {2020},
date = {2020-12-01},
urldate = {2026-02-03},
journal = {The EMBO Journal},
volume = {40},
number = {6},
pages = {EMBJ2020105496},
abstract = {Methylation 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, using Caenorhabditis elegans, we generated the first organism devoid of m5C in RNA, demonstrating that this modification is non‐essential. Using this genetic tool, we determine the localisation and enzymatic specificity of m5C 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 m5C impacts the decoding of some triplets of these two amino acids, leading to reduced translation efficiency. Upon heat stress, m5C loss leads to ribosome stalling at UUG triplets, the only codon translated by an m5C34‐modified tRNA. This leads to reduced translation efficiency of UUG‐rich transcripts and impaired fertility, suggesting a role of m5C tRNA wobble methylation in the adaptation to higher temperatures.},
keywords = {5‐methylcytosine, Caenorhabditis elegans, NSUN, RNA modifications, translation efficiency},
pubstate = {published},
tppubtype = {article}
}
Methylation 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, using Caenorhabditis elegans, we generated the first organism devoid of m5C in RNA, demonstrating that this modification is non‐essential. Using this genetic tool, we determine the localisation and enzymatic specificity of m5C 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 m5C impacts the decoding of some triplets of these two amino acids, leading to reduced translation efficiency. Upon heat stress, m5C loss leads to ribosome stalling at UUG triplets, the only codon translated by an m5C34‐modified tRNA. This leads to reduced translation efficiency of UUG‐rich transcripts and impaired fertility, suggesting a role of m5C tRNA wobble methylation in the adaptation to higher temperatures.