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Review
. 2022 Jul 15;17(7):1638-1657.
doi: 10.1021/acschembio.2c00307. Epub 2022 Jun 23.

Dihydrouridine in the Transcriptome: New Life for This Ancient RNA Chemical Modification

Damien Brégeon  1 , Ludovic Pecqueur  2 , Sabrine Toubdji  1   2 , Claudia Sudol  1   2 , Murielle Lombard  2 , Marc Fontecave  2 , Valérie de Crécy-Lagard  3   4 , Yuri Motorin  5   6 , Mark Helm  7 , Djemel Hamdane  2
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Free article
Review

Dihydrouridine in the Transcriptome: New Life for This Ancient RNA Chemical Modification

Damien Brégeon et al. ACS Chem Biol. .
Free article

Abstract

Until recently, post-transcriptional modifications of RNA were largely restricted to noncoding RNA species. However, this belief seems to have quickly dissipated with the growing number of new modifications found in mRNA that were originally thought to be primarily tRNA-specific, such as dihydrouridine. Recently, transcriptomic profiling, metabolic labeling, and proteomics have identified unexpected dihydrouridylation of mRNAs, greatly expanding the catalog of novel mRNA modifications. These data also implicated dihydrouridylation in meiotic chromosome segregation, protein translation rates, and cell proliferation. Dihydrouridylation of tRNAs and mRNAs are introduced by flavin-dependent dihydrouridine synthases. In this review, we will briefly outline the current knowledge on the distribution of dihydrouridines in the transcriptome, their chemical labeling, and highlight structural and mechanistic aspects regarding the dihydrouridine synthases enzyme family. A special emphasis on important research directions to be addressed will also be discussed. This new entry of dihydrouridine into mRNA modifications has definitely added a new layer of information that controls protein synthesis.

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