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Transcription-Wide Mapping of Dihydrouridine (D) Reveals that mRNA Dihydrouridylation is Essential for Meiotic Chromosome Segregation

61 Pages Posted: 20 Apr 2020 Publication Status: Review Complete

See all articles by Olivier Finet

Olivier Finet

University of Namur - Laboratoire de Génétique moléculaire (GéMo)

Carlo Yague-Sanz

University of Namur - Laboratoire de Génétique moléculaire (GéMo)

Lara Katharina Kruger

PSL Research University - Institut Curie

Valérie Migeot

University of Namur - Laboratoire de Génétique moléculaire (GéMo)

Felix G. M. Ernst

Université Libre de Bruxelles (ULB)

Denis L. J. Lafontaine

Université Libre de Bruxelles (ULB)

Phong Tran

PSL Research University - Institut Curie

Maxime Wéry

Université Paris VI Pierre et Marie Curie

Antonin Morillon

Université Paris VI Pierre et Marie Curie

Damien Hermand

University of Namur - Laboratoire de Génétique moléculaire (GéMo)

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Abstract

Epitranscriptomic has emerged as a fundamental control of gene expression. Nevertheless, the determination of the transcriptome-wide occupancy of RNA modifications remains challenging. We have developed Rho-seq, an integrated pipeline detecting a range of modifications through differential modification-dependent Rhodamine labeling. Using Rho-seq, we confirm that the reduction of uridine to dihydrouridine targets tRNAs in E. coli. Unexpectedly, we find that the D modification expands to mRNAs in fission yeast.The modified mRNAs are enriched for cytoskeleton-related encoding proteins. We show that the α-tubulin encoding mRNA nda2 undergoes dihydrouridylation, which affects its protein expression level. The absence of the modification onto the nda2 mRNA  impacts meiosis by inducing a metaphase delay or by completely preventing the formation of spindles during meiosis I and meiosis II, resulting in low gamete viability. Collectively these data show that the codon-specific reduction of uridine within specific mRNA is required for proper meiotic chromosome segregation and gamete viability.

Keywords: epiranscriptomics, dihydrouridine, DUS, eiosis, yeast

Suggested Citation

Finet, Olivier and Yague-Sanz, Carlo and Kruger, Lara Katharina and Migeot, Valérie and Ernst, Felix G. M. and Lafontaine, Denis L. J. and Tran, Phong and Wéry, Maxime and Morillon, Antonin and Hermand, Damien, Transcription-Wide Mapping of Dihydrouridine (D) Reveals that mRNA Dihydrouridylation is Essential for Meiotic Chromosome Segregation. Available at SSRN: https://ssrn.com/abstract=3569550 or http://dx.doi.org/10.2139/ssrn.3569550
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Olivier Finet

University of Namur - Laboratoire de Génétique moléculaire (GéMo)

Belgium

Carlo Yague-Sanz

University of Namur - Laboratoire de Génétique moléculaire (GéMo)

Belgium

Lara Katharina Kruger

PSL Research University - Institut Curie

26 rue d'Ulm
Paris cedex 05
Paris, 75248
France

Valérie Migeot

University of Namur - Laboratoire de Génétique moléculaire (GéMo)

Belgium

Felix G. M. Ernst

Université Libre de Bruxelles (ULB)

CP 132 Av FD Roosevelt 50
Brussels, Brussels 1050
Belgium

Denis L. J. Lafontaine

Université Libre de Bruxelles (ULB)

CP 132 Av FD Roosevelt 50
Brussels, Brussels 1050
Belgium

Phong Tran

PSL Research University - Institut Curie

26 rue d'Ulm
Paris cedex 05
Paris, 75248
France

Maxime Wéry

Université Paris VI Pierre et Marie Curie

175 Rue du Chevaleret
Paris, 75013
France

Antonin Morillon

Université Paris VI Pierre et Marie Curie

175 Rue du Chevaleret
Paris, 75013
France

Damien Hermand (Contact Author)

University of Namur - Laboratoire de Génétique moléculaire (GéMo) ( email )

Belgium

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