Biogenesis and intranuclear trafficking of human box C/D and H/ACA RNPs

Abstract

Box C/D and H/ACA snoRNAs represent two abundant groups of small noncoding RNAs. The majority of box C/D and H/ACA snoRNAs function as guide RNAs in the site-specific 2'-O-methylation and pseudouridylation of rRNAs, respectively. The box C/D snoRNAs associate with fibrillarin, Nop56, Nop58, and 15.5K/NHPX proteins to form functional snoRNP particles, whereas all box H/ACA snoRNAs form complexes with the dyskerin, Nop10, Nhp2, and Gar1 snoRNP proteins. Recent studies demonstrate that the biogenesis of mammalian snoRNPs is a complex process that requires numerous trans-acting factors. Most vertebrate snoRNAs are posttranscriptionally processed from pre-mRNA introns, and the early steps of snoRNP assembly are physically and functionally coupled with the synthesis or splicing of the host pre-mRNA. The maturing snoRNPs follow a complicated intranuclear trafficking process that is directed by transport factors also involved in nucleocytoplasmic RNA transport. The human telomerase RNA (hTR) carries a box H/ACA RNA domain that shares a common Cajal-body-specific localization element with a subclass of box H/ACA RNAs, which direct pseudouridylation of spliceosomal snRNAs in the Cajal body. However, besides concentrating in Cajal bodies, hTR also accumulates at a small, structurally distinct subset of telomeres during S phase. This suggests that a cell-cycle-dependent, dynamic localization of hTR to telomeres may play an important regulatory role in human telomere synthesis.