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In addition to the standard ribonucleotides, many RNA molecules contain modified nucleotides formed post-transcriptionally. Pseudouridine is formed in the context of a polyribonucleotide chain by the isomerization of uridine monophospate into pseudouridine and is the most abundant of these non-standard ribonucleotides. For that reason, it is sometimes referred to as the 'fifth ribonucleotide' of RNA, along with adenine (A), uridine (U), guanine(G), and cytosine(C) monophosphates.

In contrast to the formation of several other types of modifications where moieties are added covalently to the bases or backbone, the formation of pseudouridine from uridine is mechanistically rather complex. In order to form this modified nucleotide, the base has to be removed from the uridine monophospate, rotated, and covalently rebonded to form pseudouridine.

Most tRNAs contain modified nucleotides, tRNAs are well-known to feature this modification[1], and tRNAs are well-known to feature this modification, which are added post-transcriptionally by specific enzymes. Archaeal and Eukaryotic rRNAs are well known to be targets of guided pseudouridine formation by protein-small RNA complexes. However, recent studies have revealed many more pseudouridines exist in messenger RNA in humans than appreciated before[2][3][4].


An uppercase greek character Ψ, known as 'Psi', is often used to symbollically represent 'pseudouridine' as a single character, especially when using it along with 'A','C','G', and 'U' for the standard ribonucleotides.

Enzymatic Synthesis

See Pseudouridine synthase.


Pseudouridines have been implicated in several human diseases, such as X-linked dyskeratosis congenita, mitochondrial myopathy, and sideroblastic anemia; however, because of critical roles of the molecules being modified a direct causal link has remained to be defined[5]. With the finding of pseudouridine in many more locations among human RNAs in the last few years, there will be even more interest in relating these modifications to roles in pathologies[6].

See also


  1. Motorin Y, Helm M. tRNA stabilization by modified nucleotides. Biochemistry. 2010 Jun 22;49(24):4934-44. PMID:20459084 doi:10.1021/bi100408z
  2. Carlile TM, Rojas-Duran MF, Zinshteyn B, Shin H, Bartoli KM, Gilbert WV. Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature. 2014 Nov 6;515(7525):143-6. doi: 10.1038/nature13802. Epub 2014 Sep 5. PMID:25192136 doi:
  3. Zhao BS, He C. Pseudouridine in a new era of RNA modifications. Cell Res. 2015 Feb;25(2):153-4. doi: 10.1038/cr.2014.143. Epub 2014 Nov 4. PMID:25367125 doi:
  4. Adachi H, De Zoysa MD, Yu YT. Post-transcriptional pseudouridylation in mRNA as well as in some major types of noncoding RNAs. Biochim Biophys Acta Gene Regul Mech. 2018 Nov 8. pii: S1874-9399(18)30194-9., doi: 10.1016/j.bbagrm.2018.11.002. PMID:30414851 doi:
  5. Spenkuch F, Motorin Y, Helm M. Pseudouridine: still mysterious, but never a fake (uridine)! RNA Biol. 2014;11(12):1540-54. doi: 10.4161/15476286.2014.992278. PMID:25616362 doi:
  6. Rintala-Dempsey AC, Kothe U. Eukaryotic stand-alone pseudouridine synthases - RNA modifying enzymes and emerging regulators of gene expression? RNA Biol. 2017 Sep 2;14(9):1185-1196. doi: 10.1080/15476286.2016.1276150. Epub, 2017 Jan 3. PMID:28045575 doi:

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