Title: Transcription-wide mapping of dihydrouridine reveals that mRNA dihydrouridylation is required for meiotic chromosome segregation.
Authors: 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 L J; Hermand, Damien
Published In Mol Cell, (2022 Jan 20)
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.
PubMed ID:
34798057
MeSH Terms: Chromosome Segregation*; Chromosomes, Bacterial; Chromosomes, Fungal; Chromosomes, Human; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Escherichia coli/genetics*; Escherichia coli/metabolism; Evolution, Molecular; HCT116 Cells; Humans; Meiosis*; Oxidation-Reduction; RNA Processing, Post-Transcriptional*; RNA, Bacterial/genetics*; RNA, Bacterial/metabolism; RNA, Fungal/genetics*; RNA, Fungal/metabolism; RNA, Messenger/genetics*; RNA, Messenger/metabolism; RNA, Transfer/genetics; RNA, Transfer/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Schizosaccharomyces/genetics*; Schizosaccharomyces/metabolism; Sequence Analysis, RNA; Tubulin/genetics; Tubulin/metabolism; Uridine/metabolism*