Publications

@article{navarro_translational_2020,

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 = {https://doi.org/10.15252/embj.2020105496},

doi = {10.15252/embj.2020105496},

issn = {1460-2075},

year  = {2020},

date = {2020-12-01},

urldate = {2026-02-03},

journal = {The EMBO Journal},

volume = {40},

number = {6},

pages = {EMBJ2020105496},

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.},

keywords = {5‐methylcytosine, Caenorhabditis elegans, NSUN, RNA modifications, translation efficiency},

pubstate = {published},

tppubtype = {article}

}

@article{van_delft_profile_2017,

title = {The Profile and Dynamics of RNA Modifications in Animals},

author = {Pieter Delft and Alper Akay and Sabrina M Huber and Christoph Bueschl and Konrad L M Rudolph and Tomás Di Domenico and Rainer Schuhmacher and Eric A Miska and Shankar Balasubramanian},

url = {http://dx.doi.org/10.1002/cbic.201700093},

doi = {10.1002/cbic.201700093},

issn = {1439-4227},

year  = {2017},

date = {2017-06-01},

journal = {Chembiochem},

volume = {18},

number = {11},

pages = {979–984},

abstract = {More than a hundred distinct modified nucleosides have been identified in 

RNA, but little is known about their distribution across different 

organisms, their dynamic nature and their response to cellular and 

environmental stress. Mass-spectrometry-based methods have been at the 

forefront of identifying and quantifying modified nucleosides. However, 

they often require synthetic reference standards, which do not exist in 

the case of many modified nucleosides, and this therefore impedes their 

analysis. Here we use a metabolic labelling approach to achieve rapid 

generation of bio-isotopologues of the complete Caenorhabditis elegans 

transcriptome and its modifications and use them as reference standards to 

characterise the RNA modification profile in this multicellular organism 

through an untargeted liquid-chromatography tandem high-resolution mass 

spectrometry (LC-HRMS) approach. We furthermore show that several of these 

RNA modifications have a dynamic response to environmental stress and 

that, in particular, changes in the tRNA wobble base modification 

5-methoxycarbonylmethyl-2-thiouridine (mcm5 s2 U) lead to codon-biased 

gene-expression changes in starved animals.},

keywords = {Caenorhabditis elegans, isotopic labeling, mass spectrometry, RNA modifications, stress response, tRNA},

pubstate = {published},

tppubtype = {article}

}