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07.12.20 Miska lab find role of RNA modification m5C in C. elegans by engineering first organism to lack it

last modified Dec 16, 2020 04:46 PM
Miska lab and collagues show contribution of RNA 5-methylcytosine modification in Caenorhabditis elegans to normal fertility and to translational adaption to heat stress

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

Navarro IC et al. (2020) EMBO J Dec 7;e105496.

DOI: 10.15252/embj.2020105496. Online ahead of print.


Abstract from the paper

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.

Navarro Miska 5mC summary graphici

Summary graphic from the paper.



Read more about research in the Miska lab.

Watch Eric Miska describe his research in this short YouTube video.

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Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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