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 andH/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 functionalsnoRNP particles, whereas all box H/ACA snoRNAs form complexes with the dyskerin, Nop10, Nhp2, and Gar1 snoRNPproteins. Recent studies demonstrate that the biogenesis of mammalian snoRNPs is a complex process that requires numeroustrans-acting factors. Most vertebrate snoRNAs are posttranscriptionally processed from pre-mRNA introns, and the earlysteps of snoRNP assembly are physically and functionally coupled with the synthesis or splicing of the host pre-mRNA. Thematuring snoRNPs follow a complicated intranuclear trafficking process that is directed by transport factors also involved innucleocytoplasmic RNA transport. The human telomerase RNA (hTR) carries a box H/ACA RNA domain that shares a commonCajal-body-specific localization element with a subclass of box H/ACA RNAs, which direct pseudouridylation ofspliceosomal 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 ofhTR to telomeres may play an important regulatory role in human telomere synthesis.