page_title: Small nucleolar RNA
section_title: H/ACA box
hierarchical_section_title: Small nucleolar RNA / snoRNA guide families / H/ACA box
caption_attribution_description: English: Image has been uploaded to the Commons as part of the Molecular and Cellular Biology WikiProject in collaboration with the public-domain database Rfam. Here is the link to the discussion.
context_page_description: Small nucleolar RNAs are a class of small RNA molecules that primarily guide chemical modifications of other RNAs, mainly ribosomal RNAs, transfer RNAs and small nuclear RNAs. There are two main classes of snoRNA, the C/D box snoRNAs, which are associated with methylation, and the H/ACA box snoRNAs, which are associated with pseudouridylation.
  SnoRNAs are commonly referred to as guide RNAs but should not be confused with the guide RNAs that direct RNA editing in trypanosomes.
context_section_description: H/ACA box snoRNAs have a common secondary structure consisting of a two hairpins and two single-stranded regions termed a hairpin-hinge-hairpin-tail structure.  H/ACA snoRNAs also contain conserved sequence motifs known as H box (consensus ANANNA) and the ACA box (ACA). Both motifs are usually located in the single-stranded regions of the secondary structure. The H motif is located in the hinge and the ACA motif is located in the tail region; 3 nucleotides from the 3' end of the sequence.  The hairpin regions contain internal bulges known as recognition loops in which the antisense guide sequences (bases complementary to the target sequence) are located. These guide sequences essentially mark the location of the uridine on the target rRNA that are going to be modified. This recognition sequence is bipartite (constructed from the two different arms of the loop region) and forms complex pseudo-knots with the target RNA.  H/ACA box snoRNAs associate with four evolutionary conserved and essential proteins—dyskerin (Cbf5p), GAR1, NHP2, and NOP10—which make up the core of the H/ACA box snoRNP. Dyskerin is likely the catalytic component of the ribonucleoprotein (RNP) complex because it possesses several conserved pseudouridine synthase sequences, and is closely related to the pseudouridine synthase that modifies uridine in tRNA.  In lower eukaryotic cells such as trypanosomes, similar RNAs exist in the form of single hairpin structure and an AGA box instead of ACA box at the 3' end of the RNA. Like Trypanosomes, Entamoeba histolytica has mix population of single hairpin as well as double hairpin H/ACA box snoRNAs. It was reported that there occurred processing of the double hairpin H/ACA box snoRNA to the single hairpin snoRNAs however, unlike trypanosomes, it has regular ACA motif at 3' tail.
  The RNA component of human telomerase (hTERC) contains an H/ACA domain for pre-RNP formation and nucleolar localization of the telomerase RNP itself.  The H/ACA snoRNP has been implicated in the rare genetic disease dyskeratosis congenita (DKC) due to its affiliation with human telomerase.  Mutations in the protein component of the H/ACA snoRNP result in a reduction in physiological TERC levels.  This has been strongly correlated with the pathology behind DKC, which seems to be primarily a disease of poor telomere maintenance.
caption: Example of a H/ACA box snoRNA secondary structure taken from the Rfam database. This example is SNORA69 (RF00265).
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