Transcription-wide mapping of dihydrouridine reveals that mRNA dihydrouridylation is required for meiotic chromosome segregation
Name
nihms-1756155.pdf
Description
Accepted version
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3.18 MB
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Checksum (MD5)
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Author(s)
Finet, Olivier
Yague-Sanz, Carlo
Krüger, Lara Katharina
Tran, Phong
Migeot, Valérie
Louski, Max
Nevers, Alicia
Rougemaille, Mathieu
Sun, Jingjing
Ernst, Felix GM
Date Issued
2022
Journal
Molecular Cell
Publisher
Elsevier BV
Citation
Finet, Olivier, Yague-Sanz, Carlo, Krüger, Lara Katharina, Tran, Phong, Migeot, Valérie et al. 2022. "Transcription-wide mapping of dihydrouridine reveals that mRNA dihydrouridylation is required for meiotic chromosome segregation." Molecular Cell, 82 (2).
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.MOLCEL.2021.11.003
