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

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....

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Hauptverfasser: Cunha Navarro, Isabela (VerfasserIn) , Tuorto, Francesca (VerfasserIn) , Jordan, David (VerfasserIn) , Legrand, Carine (VerfasserIn) , Price, Jonathan (VerfasserIn) , Braukmann, Fabian (VerfasserIn) , Hendrick, Alan G (VerfasserIn) , Akay, Alper (VerfasserIn) , Kotter, Annika (VerfasserIn) , Helm, Mark (VerfasserIn) , Lyko, Frank (VerfasserIn) , Miska, Eric (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2021
In: The EMBO journal
Year: 2021, Jahrgang: 40, Heft: 6, Pages: 1-18
ISSN:1460-2075
DOI:10.15252/embj.2020105496
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/embj.2020105496
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/embj.2020105496
Volltext
Verfasserangaben:Isabela Cunha Navarro, Francesca Tuorto, David Jordan, Carine Legrand, Jonathan Price, Fabian Braukmann, Alan G Hendrick, Alper Akay, Annika Kotter, Mark Helm, Frank Lyko & Eric A Miska
Beschreibung
Zusammenfassung: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.
Beschreibung:Veröffentlicht am 7. Dezember 2020
Gesehen am 10.08.2021
Beschreibung:Online Resource
ISSN:1460-2075
DOI:10.15252/embj.2020105496

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