Regulation and Function of RNA Pseudouridylation in Human Cells

Annu Rev Genet. 2020 Nov 23:54:309-336. doi: 10.1146/annurev-genet-112618-043830. Epub 2020 Sep 1.

Abstract

Recent advances in pseudouridine detection reveal a complex pseudouridine landscape that includes messenger RNA and diverse classes of noncoding RNA in human cells. The known molecular functions of pseudouridine, which include stabilizing RNA conformations and destabilizing interactions with varied RNA-binding proteins, suggest that RNA pseudouridylation could have widespread effects on RNA metabolism and gene expression. Here, we emphasize how much remains to be learned about the RNA targets of human pseudouridine synthases, their basis for recognizing distinct RNA sequences, and the mechanisms responsible for regulated RNA pseudouridylation. We also examine the roles of noncoding RNA pseudouridylation in splicing and translation and point out the potential effects of mRNA pseudouridylation on protein production, including in the context of therapeutic mRNAs.

Keywords: RNA modification; innate immunity; mRNA; pseudouridine; snRNA; tRNA; translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Base Sequence / genetics
  • Humans
  • Intramolecular Transferases / genetics
  • Pseudouridine / genetics*
  • RNA / genetics*
  • RNA Splicing / genetics
  • RNA, Messenger / genetics

Substances

  • RNA, Messenger
  • Pseudouridine
  • RNA
  • Intramolecular Transferases
  • pseudouridine synthases