Pseudouridine

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

Pseudouridine is the most abundant RNA modification in cellular RNA. After transcription and following synthesis, RNA can be modified with over 100 chemically distinct modifications. These can potentially regulate RNA expression post-transcriptionally, in addition to the four standard nucleotides and play a variety of roles in the cell including translation, localization and stabilization of RNA. Pseudouridine, being one of them, is the C5-glycoside isomer of uridine that contains a C-C bond between C1 of the ribose sugar and C5 of uracil, rather than usual C1-N1 bond found in uridine. Uridine is converted to pseudouridine by rotating the uridine molecule 180𝄪 across its N3-C6 axis. The C-C bond gives it more rotational freedom and conformational flexibility. In addition, pseudouridine has an extra hydrogen bond donor at the N1 position.

Pseudouridine is a ubiquitous constituent of structural RNA (transfer, ribosomal, small nuclear (snRNA) and small nucleolar), and present in coding RNA, across the three phylogenetic domains of life and was the first discovered. It accounts for 4% of the nucleotides in the yeast tRNA . This base modification is able to stabilize RNA and improve base-stacking by forming additional hydrogen bonds with water through its extra imino group. There are 11 pseudouridines in the Escherichia coli rRNA, 30 in yeast cytoplasmic rRNA and a single modification in mitochondrial 21S rRNA and about 100 pseudouridines in human rRNA indicating that the extent of pseudouridylation increases with the complexity of an organism . Pseudouridine was also detected in Leishmania donovani genome. 18 pseudouridine modification sites were detected in the peptidyl transferase entry site and in the mRNA entry tunnel in protein translation. These modifications in the parasite lead to increased protein synthesis and growth rate.

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. Pseudouridine in snRNA has been shown to enhance spliceosomal RNA-pre-mRNA interaction to facilitate splicing regulation.