<p>H/ACA ribonucleoprotein particles (RNPs) are a family of RNA pseudouridine synthases that specify modification sites through guide RNAs. More than 100 mammalian H/ACA RNAs form an equal number of ribonucleoproteins (RNPs) by associating with the same four core proteins: Cbf5, Gar1, Nhp2 and Nop10. The function of these H/ACA RNPs is essential for biogenesis of the ribosome, splicing of precursor mRNAs (pre-mRNAs), maintenance of telomeres and probably for additional cellular processes [<cite idref="PUB00053435"/>]. Recent crystal structures of archaeal H/ACA protein complexes show how the same four proteins accommodate &gt;100 distinct but related H/ACA RNAs [<cite idref="PUB00036066"/>]. The complex contains a stable core composed of Cbf5 and Nop10, to which Gar1 and Nhp2 subsequently bind, the complex interacts with snoRNAs [<cite idref="PUB00053436"/>].</p><p>The crystal structure of an entire archaeal H/ACA RNP complex from <taxon tax_id="2261">Pyrococcus furiosus</taxon> has been reported at 2.3A resolution [<cite idref="PUB00036066"/>]. The complex consists of proteins Cbf5, Nop10, Gar1 and L7ae, and a single-hairpin H/ACA RNA. The RNA upper stem was bound to a composite surface formed by L7ae, Nop10 and Cbf5, and the RNA lower stem and ACA signature motif were bound to the PUA domain of Cbf5, thereby positioning middle guide sequences so that they are primed to pair with substrate RNA. Furthermore, Gar1 may regulate substrate loading and release. The overall structure rationalizes the consensus structure of H/ACA RNAs, and suggests a functional role of each protein. The structure also provides a framework for understanding the mechanism of RNA-guided pseudouridylation, as well as various cellular functions of H/ACA RNP.</p> H/ACA ribonucleoprotein complex, subunit Gar1, archaea