RNA-guided isomerization of uridine to pseudouridine--pseudouridylation

RNA Biol. 2014;11(12):1483-94. doi: 10.4161/15476286.2014.972855.


Box H/ACA ribonucleoproteins (RNPs), each consisting of one unique guide RNA and 4 common core proteins, constitute a family of complex enzymes that catalyze, in an RNA-guided manner, the isomerization of uridines to pseudouridines (Ψs) in RNAs, a reaction known as pseudouridylation. Over the years, box H/ACA RNPs have been extensively studied revealing many important aspects of these RNA modifying machines. In this review, we focus on the composition, structure, and biogenesis of H/ACA RNPs. We explain the mechanism of how this enzyme family recognizes and specifies its target uridine in a substrate RNA. We discuss the substrates of box H/ACA RNPs, focusing on rRNA (rRNA) and spliceosomal small nuclear RNA (snRNA). We describe the modification product Ψ and its contribution to RNA function. Finally, we consider possible mechanisms of the bone marrow failure syndrome dyskeratosis congenita and of prostate and other cancers linked to mutations in H/ACA RNPs.

Keywords: DC, dyskeratosis congenita; H/ACA; HH, hoyeraal-hreidarsson syndrome; PIKK, phosphatidylinositol 3-kinase-related kinase; PUA, pseudouridylase and archaeosine transglycosylase; RNA modification; RNA-guided; RNP, ribonucleoprotein; SMN, survival of motor neuron protein; SSD, SHQ1 specific domain; U, uridine; X-DC, X-linked dyskeratosis congenita; dyskeratosis congenita; prostate cancer; pseudouridine; rRNA; rRNA, ribosomal RNA; ribonucleoproteins; sca, small Cajal body; snRNA, small nuclear RNA; sno, small nucleolar; snoRNA; snoRNA, small nucleolar RNA; spliceosomal small nuclear RNA; tRNA, transfer RNA; ψ, pseudouridine, 5-ribosyluracil.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Dyskeratosis Congenita / genetics
  • Dyskeratosis Congenita / metabolism*
  • Dyskeratosis Congenita / pathology
  • Humans
  • Isomerism
  • Male
  • Mutation
  • Nucleic Acid Conformation
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Pseudouridine / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA, Guide / genetics
  • RNA, Guide / metabolism*
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism
  • RNA, Transfer, Amino Acid-Specific / genetics
  • RNA, Transfer, Amino Acid-Specific / metabolism
  • Ribonucleoproteins, Small Nuclear / genetics
  • Ribonucleoproteins, Small Nuclear / metabolism
  • Uridine / metabolism*


  • RNA, Guide
  • RNA, Ribosomal
  • RNA, Small Nuclear
  • RNA, Transfer, Amino Acid-Specific
  • Ribonucleoproteins, Small Nuclear
  • Pseudouridine
  • Uridine