Pseudouridylation-mediated gene expression modulation

Biochemical Journal, vol. 481, pp. 1–16

Abstract

RNA-guided pseudouridylation, a widespread post-transcriptional RNA modification, has recently gained recognition for its role in cellular processes such as pre-mRNA splicing and the modulation of premature termination codon (PTC) readthrough. This review provides insights into its mechanisms, functions, and potential therapeutic applications. It examines the mechanisms governing RNA-guided pseudouridylation, emphasizing the roles of guide RNAs and pseudouridine synthases in catalyzing uridine-to-pseudouridine conversion. A key focus is the impact of RNA-guided pseudouridylation of U2 small nuclear RNA on pre-mRNA splicing, encompassing its influence on branch site recognition and spliceosome assembly. Additionally, the review discusses the emerging role of RNA-guided pseudouridylation in regulating PTC readthrough, impacting translation termination and genetic disorders. Finally, it explores the therapeutic potential of pseudouridine modifications, offering insights into potential treatments for genetic diseases and cancer and the development of mRNA vaccine.

Authors 5

1. Jonathan L. Chen

   University of Rochester Medicine · University of Rochester

   Affiliation as printed

   1Department of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester Medical Center, Rochester, NY, U.S.A

2. W.‐Matthias Leeder Aachen 2ProQR Therapeutics

   ProQR Therapeutics (Netherlands)

   Affiliation as printed

   2ProQR Therapeutics, Leiden, The Netherlands

3. Pedro Morais

   Bayer (Germany)

   Affiliation as printed

   3Bayer Pharmaceuticals, Wuppertal, Germany

4. Hironori Adachi

   University of Rochester Medicine · University of Rochester

   Affiliation as printed

   1Department of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester Medical Center, Rochester, NY, U.S.A

5. Yi‐Tao Yu

   University of Rochester Medicine · University of Rochester

   Affiliation as printed

   1Department of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester Medical Center, Rochester, NY, U.S.A