Pseudouridine

Background

Creative Biolabs is dedicated to providing a full range of pseudouridine related services for our worldwide customers with years of RNA modification experience and high-end technologies.

• What Is Pseudouridine?

As one of the modified nucleoside, pseudouridine (Ψ) was the first one to be discovered as well as the most abundant RNA modification in the body. Ψ, also known as 5-β-D-ribofuranosyluracil and so-called fifth nucleoside, is the 5-ribosyl isomer of nucleoside uridine, of which the uracil of the base is linked to ribose sugar by carbon-carbon (C-C) bond rather than nitrogen carbon (N-C) glycosyl bond. Compared with the usual N-C bond found in uridine, the C-C bond structure in Ψ has greater rotational freedom. Besides, the empty N-H can serve as an additional hydrogen bond donor to participate in pairing interaction or other functional activities. These structural and functional advantages have been gradually exploited for RNA development.

Fig.1 Chemical differences between Uridine and Pseudouridine.¹

• Distributions and Functions of Pseudouridine
  As the most abundant post-transcriptional nucleoside modification, Ψ can be found in ribosomal RNA (rRNA), transfer RNA (tRNA), small nuclear RNAs (snRNA), mRNA, microRNA (miRNA), etc. The RNA modifications detection by the next-generation sequencing technology has indicated that there are 9500 putative Ψ modification sites in various RNA of most mammals, yeast, and prokaryotic organism.
  • Ψ is ubiquitous in all tRNAs, usually in D stem and anticodon stem and loop, which plays a role in the stabilization of the local structure and tertiary structure;
  • In rRNA, Ψ mainly localizes in tRNA binding site, mRNA channel, peptidyl transferase center, etc., responsible for stabilizing rRNA folding and ribosome assembly, affecting the speed and accuracy of decoding and proofreading during translation;
  • The presence of Ψ in snRNA involves in the efficiency of pre-mRNA splicing and the proper folding and assembly of the spliceosome;
  • Ψ in mRNA is indicated to affect the coding specificity of stop codons UAA, UGA, and UAG.

Fig.2 Distribution of Ψ and Ψ synthases in Homo sapiens.²

Pseudouridine Services

The properties and presence of Ψ suggest that Ψ or pseudouridylation exert significant roles in various physiological and biological activities, such as the stability of RNAs structure, ribosome diversity, translational control, even protein expression. Ψ abnormality also associates with some pathological conditions. Therefore, Ψ detection and activity analysis will provide useful information for biological stability improvement of RNA, revealing the relationship between the structure and function of modified RNA, and new therapeutic directions of some human diseases.

Creative Biolabs, a leading biotechnology company in bio-drug discovery, provides the most qualified pseudouridine modification services based on our well-established technical platform. Also, our seasoned scientists offer tailored solutions for effective epigenetic therapy development based on RNA modifications.

Highlights

• Versatility Across Applications: Pseudouridine is versatile and can be incorporated into mRNA for a variety of applications, including vaccine development, therapeutic protein production, and research purposes.
• Advanced Synthesis Techniques: We utilize sophisticated synthesis technologies to incorporate pseudouridine accurately and efficiently into mRNA, ensuring high-quality modifications every time.
• Customizable Services: Our pseudouridine services are fully customizable to meet specific research and therapeutic needs, allowing for tailored mRNA modifications that align with project objectives.
• Rigorous Quality Control: Each pseudouridine-modified mRNA product undergoes stringent quality control processes to ensure optimal purity and functionality, supporting reliable outcomes in downstream applications.

FAQ

Published Data

The article investigates the role of pseudouridine (Ψ) in RNA. It reveals that pseudouridine modifications occur during transcription in pre-mRNA, particularly in regions associated with alternative splicing. The study identifies three key pseudouridine synthases (PUS1, PUS7, and RPUSD4) that mediate these modifications, influencing alternative splicing and 3' end processing. By profiling chromatin-associated RNA, the research shows that pseudouridylation affects splicing efficiency and overlaps with RNA-binding protein sites, suggesting a regulatory role in pre-mRNA processing and gene expression.

Fig.3 Pseudouridines are enriched around splicing regulatory features and directly affect splicing.³

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References

1. Charette, M.; et al. Pseudouridine in RNA: what, where, how, and why. IUBMB Life. 2000, 49(5): 341-351.
2. Spenkuch, F.; et al. Pseudouridine: still mysterious, but never a fake (uridine)! RNA biology. 2014, 11(12), 1540-1554.
3. Martinez, Nicole M., et al. "Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing." Molecular cell 82.3 (2022): 645-659.