Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ("psi") residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme.
Mammalian H/ACA small nucleolar RNAs and telomerase RNA share common sequence and secondary structure motifs that form ribonucleoprotein particles (RNPs) with the same four core proteins, NAP57 (also dyskerin or in yeast Cbf5p), GAR1, NHP2, and NOP10. The assembly and molecular interactions of the components of H/ACA RNPs are unknown. Using in vitro transcription/translation in combination with immunoprecipitation of core proteins, UV-crosslinking, and electrophoretic mobility shift assays, we demonstrate the following. NOP10 associates with NAP57 as a prerequisite for NHP2 binding. Although NHP2 on its own binds RNA nonspecifically, this NAP57-NOP10-NHP2 core trimer specifically recognizes H/ACA RNAs. GAR1 associates independently with NAP57 near the pseudouridylase core of mature H/ACA RNPs. In contrast to other RNPs whose assembly is initiated by protein-RNA interactions, the four H/ACA core proteins form a protein-only particle that associates with H/ACA RNAs. Nonetheless, functional H/ACA snoRNPs assembled in cytosolic extracts are stable and do not exchange their RNA components, suggesting that new particle formation requires de novo synthesis.
Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Evidence
1:
Inferred from Physical InteractionUniProtKB
The human telomerase ribonucleoprotein particle (RNP) shares with box H/ACA small Cajal body (sca)RNPs and small nucleolar (sno)RNPs the proteins dyskerin, hGar1, hNhp2, and hNop10. How dyskerin, hGar1, hNhp2, and hNop10 assemble with box H/ACA scaRNAs, snoRNAs, and the RNA component of telomerase (hTR) in vivo remains unknown. In yeast, Naf1p interacts with H/ACA snoRNP proteins and may promote assembly of Cbf5p (the yeast ortholog of dyskerin) with nascent pre-snoRNAs. Here we show that the human HsQ96HR8 protein, thereafter termed hNaf1, can functionally replace endogenous Naf1p in yeast. HeLa hNaf1 associates with dyskerin and hNop10 as well as box H/ACA scaRNAs, snoRNAs, and hTR. Reduction of hNaf1 steady-state levels by RNAi significantly lowers accumulation of these components of box H/ACA scaRNP, snoRNP, and telomerase. hNaf1 is found predominantly in numerous discrete foci in the nucleoplasm and fails to accumulate within Cajal bodies or nucleoli. Altogether, these results suggest that hNaf1 intervenes in early assembly steps of human box H/ACA RNPs, including telomerase.
The intramolecular conversion of uridine to pseudouridine within an RNA molecule. This posttranscriptional base modification occurs in tRNA, rRNA, and snRNAs.
The small nucleolar ribonucleoprotein particles containing H/ACA-type snoRNAs (H/ACA snoRNPs) are crucial trans-acting factors intervening in eukaryotic ribosome biogenesis. Most of these particles generate the site-specific pseudouridylation of rRNAs while a subset are required for 18S rRNA synthesis. To understand in detail how these particles carry out these functions, all of their protein components have to be characterized. For that purpose, we have affinity-purified complexes containing epitope-tagged Gar1p protein, previously shown to be part of H/ACA snoRNPs. Under the conditions used, three polypeptides of 65, 22 and 10 kDa apparent molecular weight specifically copurify with epitope-tagged Gar1p. The 22 and 10 kDa polypeptides were identified as Nhp2p and a novel protein we termed Nop10p, respectively. Both proteins are conserved, essential and present in the dense fibrillar component of the nucleolus. Nhp2p and Nop10p are specifically associated with all H/ACA snoRNAs and are essential to the function of H/ACA snoRNPs. Cells lacking Nhp2p or Nop10p are impaired in global rRNA pseudouridylation and in the A1 and A2 cleavage steps of the pre-rRNA required for the synthesis of mature 18S rRNA. These phenotypes are probably a direct consequence of the instability of H/ACA snoRNAs and Gar1p observed in cells deprived of Nhp2p or Nop10p. Our results suggest that Nhp2p and Nop10p, together with Cbf5p, constitute the core of H/ACA snoRNPs.
Proteins conjugated with ribonucleic acid (RNA). Ribonucleoprotein are involved in a wide range of cellular processes. Besides ribosomes, in eukaryotic cells both initial RNA transcripts in the nucleus (hnRNA) and cytoplasmic mRNAs exist as complexes with specific sets of proteins. Processing (splicing) of the former is carried out by small nuclear RNPs (snRNPs). Other examples are the signal recognition particle responsible for targetting proteins to endoplasmic reticulum and a complex involved in termination of transcription.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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