title: RNA-guided isomerization of uridine to pseudouridine--pseudouridylation.
abstract: 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.
authors.affiliation: a University of Rochester Medical Center; Department of Biochemistry and Biophysics ; Center for RNA Biology ; Rochester , NY USA.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Yu
authors.forename: U Thomas
authors.initials: UT
authors.lastname: Meier
mesh_terms: D019871:Dyskeratosis Congenita / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007536:Isomerism; D008297:Male; D009154:Mutation; D009690:Nucleic Acid Conformation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011560:Pseudouridine / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism; D014529:Uridine / Q000378:metabolism*; D000094704:RNA, Guide, CRISPR-Cas Systems
chemical_list: D011560:Pseudouridine; D012335:RNA, Ribosomal; D012342:RNA, Small Nuclear; D012345:RNA, Transfer, Amino Acid-Specific; D017411:Ribonucleoproteins, Small Nuclear; D014529:Uridine; D000094704:RNA, Guide, CRISPR-Cas Systems
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