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Review
. 2022 Jan;19(1):735-750.
doi: 10.1080/15476286.2022.2078094.

The Dihydrouridine landscape from tRNA to mRNA: a perspective on synthesis, structural impact and function

Olivier Finet  1 , Carlo Yague-Sanz  1 , Florian Marchand  1 , Damien Hermand  1
Affiliations
Review

The Dihydrouridine landscape from tRNA to mRNA: a perspective on synthesis, structural impact and function

Olivier Finet et al. RNA Biol. 2022 Jan.

Abstract

The universal dihydrouridine (D) epitranscriptomic mark results from a reduction of uridine by the Dus family of NADPH-dependent reductases and is typically found within the eponym D-loop of tRNAs. Despite its apparent simplicity, D is structurally unique, with the potential to deeply affect the RNA backbone and many, if not all, RNA-connected processes. The first landscape of its occupancy within the tRNAome was reported 20 years ago. Its potential biological significance was highlighted by observations ranging from a strong bias in its ecological distribution to the predictive nature of Dus enzymes overexpression for worse cancer patient outcomes. The exquisite specificity of the Dus enzymes revealed by a structure-function analyses and accumulating clues that the D distribution may expand beyond tRNAs recently led to the development of new high-resolution mapping methods, including Rho-seq that established the presence of D within mRNAs and led to the demonstration of its critical physiological relevance.

Keywords: Dihydrouridine; Dus; RNA modification; epitranscriptome.

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Conflict of interest statement

O.F. is a consultant for Quantoom Biosciences.

Figures

Figure 1.
Figure 1.
Biochemistry of dihydrouridine.
Figure 2.
Figure 2.
Molecular fate of D upon sodium borohydride (NaBH4) or alkaline (OH−) treatments.
Figure 3.
Figure 3.
Proposed mechanism of D rhodamine labeling following sodium borohydride (NaBH4) reduction.
Figure 4.
Figure 4.
The biology of dihydrouridine.
Figure 5.
Figure 5.
Molecular strategies of bacterial Dus enzymes for substrate specificities.
See this image and copyright information in PMC

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