Pseudouridine

Pseudouridine is an isomer of uridine and the most abundant modified nucleoside in non-coding RNA. It fine-tunes and stabilizes regional structures in rRNA and tRNA, maintaining their functions in mRNA decoding, ribosome assembly, processing, and translation. Pseudouridine-modified tRNA fragments can inhibit aberrant protein synthesis and hold promise for research on myelodysplastic syndrome (MDS)-related leukemia.^{[1][2][3][4][5]}. In Vitro:Pseudouridine is one of the most abundant post-transcriptional modifications. It is formed through the isomerization of uracil, where the base rotates 180° and forms a new carbon-carbon bond with the sugar. This modification gives pseudouridine an additional hydrogen bond donor at its non-Watson-Crick edge, endowing it with chemical properties distinct from other bases^[3].
Pseudouridine, known as the fifth nucleotide, is found in all three phylogenetic domains of life. It connects the C1 of ribose and C5 of uracil, rather than the usual C1-N1 bond. Pseudouridine is generated by standalone enzymes such as pseudouridine synthases or Pus enzymes in various types of RNA, including tRNA, rRNA, small nuclear RNA (snRNA), and also in coding RNA^[4].
Pseudouridine modification stabilizes RNA, improves base stacking, and enhances structural stability by forming additional hydrogen bonds. Conserved pseudouridine modifications are found in the TΨC arm of tRNA and at several positions in rRNA, especially near the peptidyl transferase center, where they participate in the translation process^[4].