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

2021; Elsevier BV; Volume: 82; Issue: 2 Linguagem: Inglês

10.1016/j.molcel.2021.11.003

1097-4164

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

RNA and protein synthesis mechanisms

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.