Abstract
Pseudouridylation is perhaps the most common epitranscriptomic modification among over 170 known chemical RNA modifications. Pseudouridine (Ψ) is highly conserved in various stable RNAs of all organisms. RNA pseudouridylation can be catalyzed by an RNA-independent mechanism by which stand-alone enzymes, known as pseudouridine synthases, recognize the substrate and catalyze the U-to-Ψ conversion reaction. Alternatively, pseudouridylation can be catalyzed by an RNA-guided mechanism, where a guide RNA (box H/ACA RNA), which is complexed with four core proteins (Cbf5/NAP57, Nhp2, Gar1, and Nop10), site-specifically directs the conversion of target uridine into a Ψ. Here, we discuss the underlying mechanisms of pseudouridylation as well as the methods for the detection of this modification. We also discuss pseudouridylation-linked diseases and potential clinical applications of this RNA modification.
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Acknowledgments
We thank the members of the Yu lab for valuable discussions. The work performed in the Yu lab is supported by grants from the National Institute of Health (GM138387 and CA241111) and Cystic Fibrosis Foundation (YU20GO). Pedro Morais is a scientific director at ProQR Therapeutics.
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Morais, P., Adachi, H., Chen, J.L., Yu, YT. (2021). Mechanisms and Clinical Applications of RNA Pseudouridylation. In: Jurga, S., Barciszewski, J. (eds) Epitranscriptomics. RNA Technologies, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-030-71612-7_19
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