Pseudouridines in RNAs: switching atoms means shifting paradigms

Lin, Ting‐Yu; Mehta, Rahul; Glatt, Sebastian

Abstract

The structure, stability, and function of various coding and noncoding RNAs are influenced by chemical modifications. Pseudouridine (Ψ) is one of the most abundant post-transcriptional RNA base modifications and has been detected at individual positions in tRNAs, rRNAs, mRNAs, and snRNAs, which are referred to as Ψ-sites. By allowing formation of additional bonds with neighboring atoms, Ψ strengthens RNA–RNA and RNA–protein interactions. Although many aspects of the underlying modification reactions remain unclear, the advent of new transcriptome-wide methods to quantitatively detect Ψ-sites has recently changed our perception of the functional roles and importance of Ψ. For instance, it is now clear that the occurrence of Ψs appears to be directly linked to the lifetime and the translation efficiency of a given mRNA molecule. Furthermore, the administration of Ψ-containing RNAs reduces innate immune responses, which appears strikingly advantageous for the development of generations of mRNA-based vaccines. In this review, we aim to comprehensively summarize recent discoveries that highlight the impact of Ψ on various types of RNAs and outline possible novel biomedical applications of Ψ.

• Journal Article Type: Article
• Acceptance Date: Aug 22, 2021
• Online Publication Date: Sep 13, 2021
• Publication Date: 2021-09
• Deposit Date: Nov 2, 2023
• Journal: FEBS Letters
• Print ISSN: 0014-5793
• Electronic ISSN: 1873-3468
• Publisher: Federation of European Biochemical Societies
• Peer Reviewed: Peer Reviewed
• Volume: 595
• Issue: 18
• Pages: 2310-2322
• DOI: https://doi.org/10.1002/1873-3468.14188
• Keywords: Cell Biology; Genetics; Molecular Biology; Biochemistry; Structural Biology; Biophysics
• Public URL: https://durham-repository.worktribe.com/output/1875219
• Publisher URL: https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14188
• Additional Information: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) license (https://creativecommons.org/licenses/by-nc-nd/4.0).