Eukaryotic stand-alone pseudouridine synthases – RNA modifying enzymes and emerging regulators of gene expression?

ABSTRACT

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
• mRNA
• non-coding RNA
• Pus enzyme
• pseudouridine synthase
• pseudouridine
• RNA modification
• tRNA

Funding

This work was supported by Alberta Innovates Technology Futures under Grant number G201400254; and the Natural Sciences and Engineering Research Council of Canada under Grant RGPIN-2014–05954.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.