期刊
MOLECULAR CELL
卷 82, 期 2, 页码 404-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2021.11.003
关键词
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资金
- Fonds de la Recherche Nationale (F.R.S./FNRS)
- UniversiteLibre de Bruxelles (ULB)
- European Joint Programme on Rare Diseases (EJP-RD)
- Region Wallone (RiboCancer)
- International Brachet StiftuEurong (IBS)
- Agence Nationale de la Recherche (investissements d'avenir) [ANR-10-EQPX-03, ANR10-INBS-09-08]
- Canceropole Ile-de-France
- NIH [ES031529, AG063341]
- FRIA fellowship
- [PDR T.0012.14]
- [CDR J.0066.16]
- [PDR T.0112.21]
This study reveals the importance of RNA modifications in gene expression control, and develops a new integrated pipeline to detect modifications in a transcriptome-wide manner. The researchers identify a novel RNA modification and demonstrate its biological function in mRNA of fission yeast. They also find that the modification is evolutionarily conserved in human cells.
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 alpha-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.
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