Pseudouridine (5-ribosyluracil, abbreviated by the Greek letter psi- Ψ)[1] is an isomer of the nucleoside uridine in which the uracil is attached via a carbon-carbon instead of a nitrogen-carbon glycosidic bond.

[5] This base modification is able to stabilize RNA and improve base-stacking by forming additional hydrogen bonds with water through its extra imino group.

[8] Pseudouridine in rRNA and tRNA has been shown to fine-tune and stabilize the regional structure and help maintain their functions in mRNA decoding, ribosome assembly, processing and translation.

Ψ and other modified nucleotides affect the local structure of the tRNA domains they are found in without impacting the overall fold of the RNA.

This stability may increase translational accuracy by decreasing the rate of peptide bond formation and allowing for more time for incorrect codon-anticodon pairs to be rejected.

Despite Ψ’s role in local structure stabilization, pseudouridylation of tRNA is not essential for cell viability and is not usually required for aminoacylation.

Ψ residues in mRNA can affect the coding specificity of stop codons UAA, UGA, and UAG.

[12] In the SARS-CoV2 vaccine from BioNTech/Pfizer, also known as BNT162b2, tozinameran or Comirnaty, all U's have been substituted with N1-methylpseudouridine,[13] a nucleoside related to Ψ that contains a methyl group added to N1 atom.

In the ribosome Ψ residues cluster in domains II, IV, and V and stabilize RNA-RNA and/or RNA-protein interactions.

Ψ may also influence the stability of local structures which impact the speed and accuracy of decoding and proofreading during translation.

The Ψ residues in snRNAs are normally located in regions that participate in RNA-RNA and/or RNA-protein interactions involved in the assembly and function of the spliceosome.

Ψ residues in snRNAS contribute to the proper folding and assembly of the spliceosome which is essential for pre-mRNA processing.

Studies found that PUS 1 expression increased during environmental stress and is important for regulating the splicing of RNA.

The human form of PUS 4 is actually missing a binding domain called PUA or pseudouridine synthase and archaeosine trans-glycosylase.

The modification is thought to increase the stability of mRNA during heat shock before the RNA goes to the nucleus or mitochondria, but more studies are needed.

The RluA and DRAP or deaminase domain related to riboflavin synthase have completely separate functions in the protein and it is not known whether they interact with each other.

[18] An improved technique, 2-bromoacrylamide-assisted cyclization sequencing, enables Ψ-to-C transitions, for quantitative profiling of Ψ at single-base resolution.

Certain genetic mutants lacking specific pseudouridine residues in tRNA or rRNA exhibit difficulties in translation, display slow growth rates, and fail to compete effectively with wild-type strains in mixed culture.

Pseudouridine modifications are also implicated in human diseases such as mitochondrial myopathy and sideroblastic anemia (MLASA) and Dyskeratosis congenita.

Pseudouridines have been recognized as regulators of viral latency processes in human immunodeficiency virus (HIV) infections.

This property of pseudouridine was discovered by Katalin Karikó and Drew Weissman in 2005, for which they shared the 2023 Nobel Prize in Physiology or Medicine.