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.


For a long time, eukaryotic stand-alone pseudouridine synthases (Pus enzymes) were neglected as non-essential enzymes adding seemingly simple modifications to tRNAs and small nuclear RNAs. Most studies were limited to the identification and initial characterization of the yeast Pus enzymes. However, recent transcriptome-wide mapping of pseudouridines in yeast and humans revealed pervasive modification of mRNAs and other non-coding RNAs by Pus enzymes which is dynamically regulated in response to cellular stress. Moreover, mutations in at least 2 genes encoding human Pus enzymes cause inherited diseases affecting muscle and brain function. Together, the recent findings suggest a broader-than-anticipated role of the Pus enzymes which are emerging as potential regulators of gene expression. In this review, we summarize the current knowledge on Pus enzymes, generate hypotheses regarding their cellular function and outline future areas of research of pseudouridine synthases.

Keywords: Gene expression; Pus enzyme; RNA modification; mRNA; non-coding RNA; pseudouridine; pseudouridine synthase; tRNA.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Susceptibility
  • Eukaryotic Cells / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Intramolecular Transferases / genetics
  • Intramolecular Transferases / metabolism*
  • Multigene Family
  • RNA / chemistry
  • RNA / genetics*
  • RNA / metabolism*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Nuclear / chemistry
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism
  • RNA, Transfer / chemistry
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism
  • RNA, Untranslated / chemistry
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism
  • Substrate Specificity


  • RNA, Messenger
  • RNA, Small Nuclear
  • RNA, Untranslated
  • RNA
  • RNA, Transfer
  • Intramolecular Transferases
  • pseudouridine synthases