Pseudouridylation (Ψ) Machinery

Although pseudouridylation (Ψ) is one of the most widespread modifications of ribosomal RNA (rRNA), much remains to be understood about the mechanism and impact of this modification. As a leader in ribosome services, Creative Biolabs focuses on providing customers with Ψ related background information and cost-effective ribosome and rRNA analysis services to facilitate the research process of your project.

Introduction to Ψ

RNA modifications play significant roles in many biological processes. They can regulate the fate of RNA molecules, at the cellular and biological levels, such as cell differentiation and sex determination. Ψ, the C-glycoside isomer of uridine, is the most common single-nucleotide modification in functional RNAs, frequently occurring in highly conserved regions of RNAs. Scientists have discovered that many Ψ sites are located at key ribosomal sites, such as tRNA and mRNA binding sites. Ψ is present in almost all species and various types of RNA, including rRNA, transfer RNA (tRNA), small nucleolar RNA (snoRNA), and messenger RNA (mRNA).

Fig.1 Structure formulae of uridine and pseudouridine. (Penzo, 2018)

Importance of Ψ

Ψ, along with other rRNA modifications, is thought to be critical for ribosome production, as a feature of this process is the presence of multiple regulatory steps that ultimately ensure the production of qualified ribosomes. Studies have shown that this modification is closely related to ribosomal activity. For example, in eukaryotes, Ψ residues tend to cluster in critical regions of the ribosome. Base modifications in rRNA are highly conserved and associated with vital functional domains of the ribosome, suggesting that Ψ contributes significantly to proper ribosomal performance. Furthermore, Ψ is important for translational fidelity in eukaryotes. Scientists speculate that Ψ is an essential component of proper RNA folding and function. In particular, the presence of Ψ can affect RNA structure, and ultimately its functional properties. Ribosomal RNA modifications are considered to be one of the major sources of ribosomal heterogeneity, both under physiological and pathological conditions.

Ψ and Disease

The first evidence linking human disease and rRNA Ψ was found in patients with X-linked dyskeratosis congenita (X-DC) with mutations in the gene encoding pseudouridine synthase. These observations highlight the impact of reduced rRNA Ψ on translational control and may help explain the defects in proliferating tissues and the typical cancer susceptibility of X-DCs. Recently, high-resolution structural cryo-electron microscopy studies have revealed that in human ribosomes, rRNA modifications are altered in cancer cells. These findings provide new insights into the relevance of rRNA Ψ in ribosomal function and cancer.

The importance of rRNA Ψ and its regulation has not been fully explored for many reasons. With our professional knowledge and advanced experimental platform, we can provide global customers with comprehensive ribosome and related factor analysis services. If you have the requirements for ribosome analysis, Creative Biolabs is your best choice. Please contact us for more details.

Reference

1. Penzo, M.; Montanaro, L. Turning uridines around: Role of rRNA pseudouridylation in ribosome biogenesis and ribosomal function. Biomolecules. 2018, 8(2): 38.