Mechanistic insight into the pseudouridylation of RNA

Ting-Yu Lin; Yasmin Stone; Sebastian Glatt

doi:10.1080/15476286.2025.2541421

Mechanistic insight into the pseudouridylation of RNA

Title (eng)

Mechanistic insight into the pseudouridylation of RNA

Author

Ting-Yu Lin

Yasmin Stone

Sebastian Glatt

University of Veterinary Medicine Vienna

Abstract (eng)

Pseudouridylation (Ψ) is a highly abundant and conserved RNA modification that is present in all three domains of life. The incorporation of Ψ can affect the stability of RNAs, modulate their interaction patterns, and regulate many other aspects of RNA biology. Ψ are introduced by a structurally highly related enzyme family, called pseudouridine synthases (PUS). Each PUS enzyme targets distinct RNA substrates and target sites. Dysregulation of PUS enzymes has been implicated in neurodevelopmental disorders, mitochondrial diseases and cancer. These clinical consequences highlight the ultimate need to understand how these enzymes catalyze their modification reactions and achieve target selectivity as well as specificity. In this review, we summarize the currently available structural information on PUS enzymes and highlight the most recent progress in understanding some underlying mechanistic principles. Furthermore, we illustrate the increasing therapeutic applications related to the so-called 5th RNA base.

Keywords (eng)

PseudouridinetRNARNA ModificationPseudouridine SynthaseCryo-electron MicroscopyCrystallographyNeurodegenerative DiseaseCancer

Type (eng)

journal article

Language

[eng]

Persistent identifier

https://phaidra.vetmeduni.ac.at/o:4844

DOI

10.1080/15476286.2025.2541421

Is in series

Title (eng)