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| Status |
Public on Jun 30, 2020 |
| Title |
Translational adaptation to heat stress is mediated by 5-methylcytosine RNA modification in Caenorhabditis elegans |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
In order to fulfil a wide range of cellular functions, RNA molecules contain, in addition to the four canonical bases, a large number of chemically modified structures. Among those, the methylation of carbon-5 of cytosines (m5C) is an abundant, widespread mark in different classes of RNAs. m5C is catalysed by DNMT2 and by seven members of the NSUN family of enzymes. While some m5C-methyltransferases have been studied individually and implicated in phenotypes observed in organisms ranging from yeast to humans, it remains unclear how the m5C methylome acts to sustain development in homeostasis and stress. Here, using Caenorhabditis elegans as a model organism, we developed the first organism devoid of detectable m5C in RNA, providing strong evidence that this modification and its derivatives are non-essential for the nematode’s development and fertility under standard laboratory conditions. We further used this genetic tool to determine the localisation of m5C sites in different RNA classes, and showed that NSUN-4 acts as a multisite-specific tRNA/rRNA methyltransferase in the mitochondria. In addition, we show that m5C is required for adaptation to temperature changes, as animals devoid of this modification present temperature-sensitive fertility defects. At the molecular level, we show that loss of m5C leads to increased ribosome pausing at triplets encoding for leucine and proline, the most frequently methylated tRNA isoacceptors in C. elegans. This is correlated with reduced translation efficiency of transcripts enriched in these amino acids. Finally, we found translation of Leu-UUG codons to be the most strongly affected upon heat shock, suggesting a role of m5C wobble methylation in the adaptation to heat stress.
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| Overall design |
RNASeq and Ribosome profilling from 4 samples of C. elegans. WT and NSUN mutants from 20 and 27 degrees celcius.
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| Contributor(s) |
Navarro IC, Tuorto F, Jordan D, Legrand C, Price J, Braukmann F, Hendrick A, Akay A, Kotter A, Helm M, Lyko F, Miska EA |
| Citation(s) |
33283887 |
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| Submission date |
Mar 03, 2020 |
| Last update date |
Aug 09, 2021 |
| Contact name |
Jonathan Lewis Price |
| Organization name |
University of Cambridge
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| Department |
The Gurdon Inst.
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| Lab |
Miska Lab
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| Street address |
The Gurdon Inst. Tennis Court Road
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| City |
cambridge |
| ZIP/Postal code |
CB2 1QN |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL13657 |
Illumina HiSeq 2000 (Caenorhabditis elegans) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA609901 |
| SRA |
SRP251352 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE146256_RAW.tar |
1.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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