• Citer

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

par Finet, Olivier;Yague-Sanz, Carlo;Krüger, Lara Katharina;Tran, Phong;Migeot, Valérie;Louski, Max;Nevers, Alicia;Rougemaille, Mathieu;Sun, Jingjing;Ernst, Felix G.M.;Wacheul, Ludivine ;Wery, Maxime ;Morillon, Antonin;Dedon, Peter;Lafontaine, Denis ;Hermand, Damien
Référence Molecular cell, 82, 2, page (404-419.e9)
Publication Publié, 2022-01-01

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

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.