2. Academic Validation
  3. Transcription-wide mapping of dihydrouridine reveals that mRNA dihydrouridylation is required for meiotic chromosome segregation

Transcription-wide mapping of dihydrouridine reveals that mRNA dihydrouridylation is required for meiotic chromosome segregation

  • Mol Cell. 2022 Jan 20;82(2):404-419.e9. doi: 10.1016/j.molcel.2021.11.003.
Olivier Finet 1,  Carlo Yague-Sanz 1,  Lara Katharina Krüger 2,  Phong Tran 2,  Valérie Migeot 1,  Max Louski 1,  Alicia Nevers 3,  Mathieu Rougemaille 3,  Jingjing Sun 4,  Felix G M Ernst 5,  Ludivine Wacheul 5,  Maxime Wery 6,  Antonin Morillon 6,  Peter Dedon 4,  Denis L J Lafontaine 5,  Damien Hermand 7
Affiliations

Affiliations

  • 1 URPHYM-GEMO, The University of Namur, Namur 5000, Belgium.
  • 2 Institut Curie, PSL Research University, CNRS, UMR 144, Paris, France.
  • 3 Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette 91198, France.
  • 4 Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA.
  • 5 RNA Molecular Biology, Fonds de la Recherche Scientifique (F.R.S./FNRS), Université Libre de Bruxelles, Charleroi-Gosselies, Belgium.
  • 6 ncRNA, epigenetic and genome fluidity, Institut Curie, PSL Research University, CNRS UMR 3244, Université Pierre et Marie Curie, Paris, France.
  • 7 URPHYM-GEMO, The University of Namur, Namur 5000, Belgium. Electronic address: damien.hermand@unamur.be.
PMID: 34798057 DOI: 10.1016/j.molcel.2021.11.003
Abstract

The epitranscriptome has emerged as a new fundamental layer of control of gene expression. Nevertheless, the determination of the transcriptome-wide occupancy and function of RNA modifications remains challenging. Here 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 (D) by the Dus reductase Enzymes targets tRNAs in E. coli and fission yeast. We find that the D modification is also present on fission yeast mRNAs, particularly those encoding cytoskeleton-related proteins, which is supported by large-scale proteome analyses and ribosome profiling. We show that the α-tubulin encoding mRNA nda2 undergoes Dus3-dependent dihydrouridylation, which affects its translation. The absence of the modification on nda2 mRNA strongly impacts meiotic chromosome segregation, resulting in low gamete viability. Applying Rho-seq to human cells revealed that tubulin mRNA dihydrouridylation is evolutionarily conserved.

Keywords

DUS; dihydrouridine; epitranscriptomics; meiosis; yeast.

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