2021
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: EMBO J., vol. 40, no. 6, pp. e105496, 2021, ISSN: 0261-4189, (Publisher: John Wiley & Sons, Ltd).
Abstract | Links | BibTeX | Tags: 5-methylcytosine, Caenorhabditis elegans, NSUN, RNA modifications, translation efficiency
@article{navarro_translational_2021,
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 = {http://dx.doi.org/10.15252/embj.2020105496},
doi = {10.15252/embj.2020105496},
issn = {0261-4189},
year = {2021},
date = {2021-03-01},
journal = {EMBO J.},
volume = {40},
number = {6},
pages = {e105496},
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.},
note = {Publisher: John Wiley & Sons, Ltd},
keywords = {5-methylcytosine, Caenorhabditis elegans, NSUN, RNA modifications, translation efficiency},
pubstate = {published},
tppubtype = {article}
}
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.
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.