Posttranscriptional RNA Pseudouridylation

Pseudouridine (Ψ) is the most abundant posttranscriptional modification in noncoding RNAs. Pseudouridines are often clustered in important regions of rRNAs (ribosomal RNAs), snRNAs (small nuclear RNAs), and tRNAs (transfer RNAs), contributing to RNA function. Pseudouridylation is governed by two independent mechanisms. The first involves single protein enzymes called pseudouridine synthases (PUSs) that alone recognize the substrate and catalyze the isomerization of uridine to pseudouridine (RNA-independent pseudouridylation). The second is an RNA-guided pseudouridylation by a family of box H/ACA RNPs (ribonucleoproteins), each of which consists of a unique RNA (box H/ACA RNA) and four common core proteins (Cbf5/NAP57/Dyskerin, Nhp2/L7Ae, Nop10, and Gar1). The RNA component serves as a guide that base pairs with the substrate RNA and directs the enzyme (Cbf5) to carry out the pseudouridylation reaction at a specific site. The crystal structures of many PUSs have been solved in numerous organisms including E. coli and human. Several partial and complete crystal structures of archaea and yeast box H/ACA RNPs are available, providing a rich source of information regarding the molecular interactions between protein components and box H/ACA RNA. Over the years, several experimental systems have been developed to study the mechanism and function of pseudouridylation. Apart from noncoding RNA pseudouridylation, recent experiments have provided evidence of mRNA pseudouridylation as well. Despite remarkable progress, there is a need to accelerate efforts in order to understand the detailed mechanisms and functions of RNA pseudouridylation.