A Well-Connected and Conserved Nucleoplasmic Helicase Is Required for Production of Box C/D and H/ACA snoRNAs and Localization of snoRNP Proteins

Abstract

Synthesis of small nucleolar RNA protein complexes (snoRNPs) occurs in several stages, which are almost certainly overlapping (for recent summaries, see references 66 and 81). The major phases include (i) synthesis of the snoRNA and protein components, (ii) assembly of the snoRNP, and (iii) movement of the particle to the nucleolar complex, perhaps by way of Cajal bodies (22,45,54,58). In metazoans, most snoRNAs are derived from introns of protein genes, and all of the assembly steps are believed to occur in the nucleoplasm. In Saccharomyces cerevisiae, most snoRNAs are transcribed from independent genes; however, a few are encoded in introns (81). Processing of the pre-snoRNAs in yeast is coupled to mRNA splicing (50, 53), and this situation likely pertains to metazoans as well.Successful progression of the snoRNA transcript through each biosynthetic stage depends on the box C/D and H/ACA sequences used to classify the two large families of snoRNPs (see, e.g., references 8, 13, 14, 19, 27, 38, 39, 44, 45, 58, 64, and 79). In vivo function studies have shown that the binding of proteins to the motifs defined by the box elements is essential for proper processing of the snoRNA (end formation) and its localization to the nucleolus, presumably as a nascent snoRNP (reviewed in references 35, 66, and 81). Current models propose that protein binding to these motifs may be the first step in snoRNP assembly. Notably, the box elements are also intimately involved in the two types of nucleotide modification reaction mediated by the snoRNPs, i.e., ribose methylation by the C/D snoRNPs and pseudouridine formation by the H/ACA snoRNPs (4-6, 18, 34, 47, 66).The final list of factors involved in snoRNP synthesis and function will probably be quite extensive. For example snoRNA processing involves several nucleases, some of which also participate in the processing of rRNA, other small RNAs, and pre-mRNA (72; see also references 2, 15, 16, and 71).

Assembly of the Archaeal Box C/D sRNP Can Occur via Alternative Pathways and Requires Temperature-facilitated sRNA Remodeling

“…[52][53][54] Box C/D snoRNP biogenesis in yeast requires Tip48 and Tip49 helicases whose presumed function is the rearrangement of RNA folded structures during RNP assembly. 25,[55][56][57] Similarly, the human U3 snoRNA is associated with these same helicases during RNP biogenesis in the nucleoplasm. 57 RNA helicases are abundant in all kingdoms of life, suggesting that this class of proteins likely plays important structural roles in the biogenesis and function of numerous RNP complexes.…”

The R2TP chaperone complex: its involvement in snoRNP assembly and tumorigenesis

“…Additionally, given that all core protein factors of box H/ACA snoRNP also assembles with TERC (telomerase RNA component), forming TERCcontaining RNP (34), its biogenesis could follow that of canonical box H/ACA snoRNPs by involving R2TP (17). In yeast, Rvbs are involved in box H/ACA snoRNP biogenesis (6,40), although the contribution of Pih1 and Tah1 to the process, if any, remains unknown.…”

Mechanism of the AAA+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs

“…Additional factors implicated in the biogenesis of H/ACA RNPs are the two closely related proteins pontin and reptin that belong to the AAA+ superfamily of ATPases (ATPases associated with diverse cellular activities) (King et al 2001;Boulon et al 2008;Venteicher et al 2008;Zhao et al 2008). Pontin and reptin have been implicated in a staggering array of basic cellular processes and carry a nearly equal number of different names, including TIP49a/b, Pontin52/ Reptin52, TIP49/48, RUVBL1/2, p55/ 50, and NMP238 in metazoans, and Rvb1/2, Tip49/48, and Tih1/2 in yeast.…”