Format:
18
ISSN:
1460-2075
Content:
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.
Note:
Veröffentlicht am 7. Dezember 2020
,
Gesehen am 10.08.2021
In:
European Molecular Biology Organization, The EMBO journal, [London] : Nature Publishing Group UK, 1982, 40(2021), 6, Artikel-ID e105496, Seite 1-18, 1460-2075
In:
volume:40
In:
year:2021
In:
number:6
In:
elocationid:e105496
In:
pages:1-18
In:
extent:18
Language:
English
DOI:
10.15252/embj.2020105496
URL:
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