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

• Published in: RNA Biology
• Main Authors: Olivier Finet, Carlo Yague-Sanz, Florian Marchand, Damien Hermand
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2022-12-01
• Subjects: rna modification; dihydrouridine; dus; epitranscriptome
• Online Access: http://dx.doi.org/10.1080/15476286.2022.2078094
• ISSN: 1547-6286; 1555-8584

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.