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

Olivier Finet, Carlo Yague-Sanz, Lara Katharina Krüger, Phong Tran, Valérie Migeot, Max Louski, Alicia Nevers, Mathieu Rougemaille, Jingjing Sun, Felix G M Ernst, Ludivine Wacheul, Maxime Wery, Antonin Morillon, Peter Dedon, Denis L J Lafontaine, Damien Hermand

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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.

langue originaleAnglais
Pages (de - à)404-419.e9
journalMolecular Cell
Volume82
Numéro de publication2
Date de mise en ligne précoce18 nov. 2021
Les DOIs
Etat de la publicationPublié - 20 janv. 2022

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