“…Structure of the pre-rRNA and processing pathway in Saccharomyces cerevisiae. A: Structure of the 35S pre-rRNA+ The 35S operon contains the sequences for the mature 18S, 5+8S, and 25S rRNAs separated by the two internal transcribed spacers (ITS1 and ITS2)+ In addition, two external transcribed spacers, the 59ETS and 39ETS, are present at either end+ B: Pre-rRNA processing pathway+ The 35S pre-rRNA undergoes sequential processing reactions to generate the mature rRNAs+ Cleavage at A0 generates the 33S pre-rRNA+ It is subsequently cleaved at sites A1 at the 59 end of the 18S rRNA giving rise to the 32S pre-rRNA, and A2 in ITS1 yielding the 20S and 27SA2 pre-rRNAs+ The latter two species are precursors for the rRNAs respectively found in the small and large ribosomal subunits+ The 20S pre-rRNA is endonucleolytically cleaved at site D to produce the 18S rRNA+ The 27SA2 intermediate is processed by two alternative pathways+ In the major pathway, 27SA2 is cleaved by RNase MRP at site A3 in ITS1 yielding 27SA3, which is trimmed by 5939 exonucleases Rat1p and Xrn1p to site B1 S , generating the 27SB S precursor+ Approximately 15% of the 27SA2 molecules are processed at site B1 L , producing the 27SB L pre-rRNA+ 27SB S and 27SB L molecules are then processed at sites C1 and C2, yielding mature 25S rRNA and the 7S S and 7S L pre-rRNAs respectively, which are converted to 5+8S S and 5+8S L rRNAs by a complex of 39 59 exoribonucleases, the "exosome+" shifted to their associated proteins+ C/D snoRNPs are now known to contain three common essential proteins, Nop1p/fibrillarin (Tyc & Steitz, 1989, Baserga et al+, 1991Peculis & Steitz, 1994;Ganot et al+, 1997b), Nop56p, and Nop58p/Nop5p (Gautier et al+, 1997;Wu et al+, 1998, Lafontaine & Tollervey, 1999, whereas H/ACA snoRNPs contain at least four, Cbf5p (Jiang et al+, 1993;Cadwell et al+, 1997;, Gar1p (Girard et al+, 1992, Ganot et al+, 1997bHenras et al+, 1998), Nhp2p (Henras et al+, 1998;Watkins et al+, 1998), and Nop10p (Henras et al+, 1998)+ The discovery that Cbf5p, which is highly related to pseudouridine synthases (Koonin, 1996), is an integral snoRNP component strongly suggests that H/ACA snoRNPs not only select, but also modify prerRNA uridine residues )+ C/D snoRNPs also probably catalyze pre-rRNA modifications, as it has recently been noticed that the first characterized snoRNP protein component, Nop1p/ fibrillarin, contains the conserved methyltransferase motifs (Niewmierzycka & Clarke, 1999)+ SnoRNPs need to be able to reversibly interact with the pre-rRNA to catalyze pre-rRNA modifications or to promote pre-rRNA cleavage events+ Little is known about the ways snoRNPs/pre-rRNA interactions are modulated+ In the absence of the Gar1p protein, so-called because it contains two glycine/arginine-rich (GAR) domains at its N-and C-ter...…”