MetaCyc Pathway: pseudouridine degradation
Inferred from experiment

Enzyme View:

Pathway diagram: pseudouridine degradation

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Degradation/Utilization/AssimilationNucleosides and Nucleotides DegradationPurine Nucleotides Degradation

Some taxa known to possess this pathway include : Agrobacterium tumefaciens, Escherichia coli UTI89, Tetrahymena pyriformis, Thermotoga maritima

Expected Taxonomic Range: Bacteria , Eukaryota

A bewildering number of post-transcriptional modifications are introduced into cellular RNAs by different enzymes [FerreDAmare03]. The most abundant post-transcriptional nucleobase modification in cellular RNAs is the isomerization of uridine to pseudouridine, which is carried out by the enzyme pseudouridine synthase in a reaction that does not require any cofactors. In pseudouridine uracil is bound to the to ribose through C5 rather than through N1 as is the case for uridine. The synthase severs the normal glycosidic C-N bond of uridine, flips the uracil moiety along its N3-C6 axis, and forms a glycosidic C-C bond with C5. Pseudouridine is one of few molecules that have a glycosidic C-C bond.

Pseudouridine synthases belong to four different families, which are represented in Escherichia coli by the truA, truB, rluA and rsuA. The only sequence element that is absolutely conserved among the four families of enzymes is a catalytic aspartic acid [Huang98, Del01, Ramamurthy99].

Pseudouridylation is found in organisms from all kingdoms. Mammalian rRNA contains about 100 pseudouridines per ribosome, and tRNAs contain an average of 3 - 4 pseudouridines. While many eukaryotes possess the ability to degrade pseudouridine, mammals appear to have lost this ability, and pseudouridine is excreted in their urine.

Pseudouridine has been shown to serve as a source of uracil for a strain of Escherichia coli that is deficient in pyrimidine synthesis [Breitman68]. It was shown that pseudouridine was first phosphorylated by a kinase to pseudouridine 5'-phosphate [Solomon71], followed by hydrolysis to D-ribose 5-phosphate and uracil [Breitman70]. The genes encoding these two enzymes have been discovered in Escherichia coli UTI89, a uropathogenic strain [Preumont08]. The genes were cloned, and the enzymes were purified and characterized, conforming the proposed function.

Similar genes were found in the genomes of many bacteria and almost all eukaryotes [Preumont08].

Variants: purine deoxyribonucleosides degradation I, purine deoxyribonucleosides degradation II, purine nucleobases degradation I (anaerobic), purine nucleobases degradation II (anaerobic), purine nucleotides degradation I (plants), purine nucleotides degradation II (aerobic), purine ribonucleosides degradation, urate biosynthesis/inosine 5'-phosphate degradation

Unification Links: EcoCyc:PWY-6019

Created 27-Aug-2008 by Caspi R, SRI International


Breitman68: Breitman TR, Scher CD (1968). "Growth of pyrimidineless strains of Escherichia coli on 5-ribosyluracil (pseudouridine)." J Bacteriol 96(5);1873-4. PMID: 4882030

Breitman70: Breitman TR (1970). "Pseudouridulate synthetase of Escherichia coli: correlation of its activity with utilization of pseudouridine for growth." J Bacteriol 103(1);263-4. PMID: 4912525

Del01: Del Campo M, Kaya Y, Ofengand J (2001). "Identification and site of action of the remaining four putative pseudouridine synthases in Escherichia coli." RNA 7(11);1603-15. PMID: 11720289

FerreDAmare03: Ferre-D'Amare AR (2003). "RNA-modifying enzymes." Curr Opin Struct Biol 13(1);49-55. PMID: 12581659

Huang98: Huang L, Pookanjanatavip M, Gu X, Santi DV (1998). "A conserved aspartate of tRNA pseudouridine synthase is essential for activity and a probable nucleophilic catalyst." Biochemistry 37(1);344-51. PMID: 9425056

Preumont08: Preumont A, Snoussi K, Stroobant V, Collet JF, Van Schaftingen E (2008). "Molecular identification of pseudouridine metabolizing enzymes." J Biol Chem 283(37):25238-46. PMID: 18591240

Ramamurthy99: Ramamurthy V, Swann SL, Paulson JL, Spedaliere CJ, Mueller EG (1999). "Critical aspartic acid residues in pseudouridine synthases." J Biol Chem 274(32);22225-30. PMID: 10428788

Solomon71: Solomon LR, Breitman TR (1971). "Pseudouridine kinase of escherichia coli: a new enzyme." Biochem Biophys Res Commun 44(2);299-304. PMID: 4334133

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Charette00: Charette M, Gray MW (2000). "Pseudouridine in RNA: what, where, how, and why." IUBMB Life 49(5);341-51. PMID: 10902565

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Snyder04: Snyder JA, Haugen BJ, Buckles EL, Lockatell CV, Johnson DE, Donnenberg MS, Welch RA, Mobley HL (2004). "Transcriptome of uropathogenic Escherichia coli during urinary tract infection." Infect Immun 72(11);6373-81. PMID: 15501767

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 20.0 (software by SRI International) on Fri May 6, 2016, BIOCYC14.