Pseudouridine

Pseudouridine
Names
IUPAC name
5-(β-D-Ribofuranosyl)pyrimidine-2,4(1H,3H)-dione
Systematic IUPAC name
5-[(2S,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4(1H,3H)-dione
Other names
psi-Uridine, 5-Ribosyluracil, beta-D-Pseudouridine, 5-(beta-D-Ribofuranosyl)uracil
Identifiers
3D model (JSmol)
32779
ChEBI
ChEMBL
ChemSpider
KEGG
UNII
  • InChI=1S/C9H12N2O6/c12-2-4-5(13)6(14)7(17-4)3-1-10-9(16)11-8(3)15/h1,4-7,12-14H,2H2,(H2,10,11,15,16)/t4-,5-,6-,7+/m1/s1 checkY
    Key: PTJWIQPHWPFNBW-GBNDHIKLSA-N checkY
  • InChI=1/C9H12N2O6/c12-2-4-5(13)6(14)7(17-4)3-1-10-9(16)11-8(3)15/h1,4-7,12-14H,2H2,(H2,10,11,15,16)/t4-,5-,6-,7+/m1/s1
    Key: PTJWIQPHWPFNBW-GBNDHIKLBY
  • InChI=1S/C9H12N2O6/c12-2-4-5(13)6(14)7(17-4)3-1-10-9(16)11-8(3)15/h1,4-7,12-14H,2H2,(H2,10,11,15,16)/t4-,5-,6-,7+/m1/s1
    Key: PTJWIQPHWPFNBW-GBNDHIKLSA-N
  • O=C1N\C=C(/C(=O)N1)[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O
Properties
C9H12N2O6
Molar mass 244.20 g/mol
Appearance White granular powder
Highly soluble in water.
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

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.

Pseudouridine is the most abundant RNA modification in cellular RNA[2] and one of over 100 chemically distinct modifications that may affect translation or other functions of RNA. Pseudouridine 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.[3] The C-C bond gives it more rotational freedom and conformational flexibility.[4] 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 mRNA, across the three phylogenetic domains of life and was the first discovered. It accounts for 4% of the nucleotides in yeast tRNA.[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.[6] There are 11 pseudouridines in 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.[7] Pseudouridine was also detected in the 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.[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.[4][9][10] Pseudouridine in snRNA has been shown to enhance spliceosomal RNA-pre-mRNA interaction to facilitate splicing regulation.[11]

Pseudouridine is biosynthesized from uridine via the action of Ψ synthases.
  1. ^ Hamma, Tomoko; Ferré-D'Amaré, Adrian R. (November 2006). "Pseudouridine Synthases". Chemistry & Biology. 13 (11): 1125–1135. doi:10.1016/j.chembiol.2006.09.009. ISSN 1074-5521. PMID 17113994.
  2. ^ Penzo, Marianna; Guerrieri, Ania; Zacchini, Federico; Treré, Davide; Montanaro, Lorenzo (2017-11-01). "RNA Pseudouridylation in Physiology and Medicine: For Better and for Worse". Genes. 8 (11): 301. doi:10.3390/genes8110301. ISSN 2073-4425. PMC 5704214. PMID 29104216.
  3. ^ Garus A, Autexier C (2021). "Dyskerin: an essential pseudouridine synthase with multifaceted roles in ribosome biogenesis, splicing, and telomere maintenance". RNA. 27 (12): 1441–1458. doi:10.1261/rna.078953.121. PMC 8594475. PMID 34556550.
  4. ^ a b Gray, Michael Charette, Michael W. (2000-05-01). "Pseudouridine in RNA: What, Where, How, and Why". IUBMB Life. 49 (5): 341–351. doi:10.1080/152165400410182. ISSN 1521-6543. PMID 10902565. S2CID 20561376.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Davis, F. F.; Allen, F. W. (October 1957). "Ribonucleic acids from yeast which contain a fifth nucleotide". The Journal of Biological Chemistry. 227 (2): 907–915. ISSN 0021-9258. PMID 13463012.
  6. ^ Davis, Darrell R. (1995). "Stabilization of RNA stacking by pseudouridine". Nucleic Acids Research. 23 (24): 5020–5026. doi:10.1093/nar/23.24.5020. ISSN 0305-1048. PMC 307508. PMID 8559660.
  7. ^ Ofengand, J; Bakin, A (1997-02-21). "Mapping to nucleotide resolution of pseudouridine residues in large subunit ribosomal RNAs from representative eukaryotes, prokaryotes, archaebacteria, mitochondria and chloroplasts". Journal of Molecular Biology. 266 (2): 246–268. doi:10.1006/jmbi.1996.0737. PMID 9047361.
  8. ^ Bussotti, Giovanni; Piel, Laura; Pescher, Pascale; Domagalska, Malgorzata A.; Rajan, K. Shanmugha; Cohen-Chalamish, Smadar; Doniger, Tirza; Hiregange, Disha-Gajanan; Myler, Peter J.; Unger, Ron; Michaeli, Shulamit; Späth, Gerald F. (21 December 2021). "Genome instability drives epistatic adaptation in the human pathogen Leishmania". Proceedings of the National Academy of Sciences. 118 (51): e2113744118. Bibcode:2021PNAS..11813744B. doi:10.1073/pnas.2113744118. ISSN 0027-8424. PMC 8713814. PMID 34903666.
  9. ^ Ge, Junhui; Yu, Yi-Tao (April 2013). "RNA pseudouridylation: new insights into an old modification". Trends in Biochemical Sciences. 38 (4): 210–218. doi:10.1016/j.tibs.2013.01.002. ISSN 0968-0004. PMC 3608706. PMID 23391857.
  10. ^ Rintala-Dempsey, Anne C.; Kothe, Ute (2017-01-03). "Eukaryotic stand-alone pseudouridine synthases – RNA modifying enzymes and emerging regulators of gene expression?". RNA Biology. 14 (9): 1185–1196. doi:10.1080/15476286.2016.1276150. ISSN 1547-6286. PMC 5699540. PMID 28045575.
  11. ^ Wu, Guowei; Radwan, Mohamed K.; Xiao, Mu; Adachi, Hironori; Fan, Jason; Yu, Yi-Tao (2016-06-07). "TheTORsignaling pathway regulates starvation-induced pseudouridylation of yeast U2 snRNA". RNA. 22 (8): 1146–1152. doi:10.1261/rna.056796.116. ISSN 1355-8382. PMC 4931107. PMID 27268497.