The small nucleolar RNAs (snoRNAs) are stable RNAs that are found within small nucleolar ribonucleoprotein complexes (snoRNPs) and localized to the nucleoli of eukaryotic cells. The majority of the snoRNAs are involved in ribosomal RNA processing, though some are also involved in processing of other RNAs and a couple have not yet been characterized as to their role in cells. Based on conserved sequence elements and association with conserved nucleolar proteins, the snoRNAs can be divided into three classes: box C/D snoRNAs, box H/ACA snoRNAs, and snoRNA MRP. Both the box C/D and box H/ACA families have many members, while MRP (produced by the NME1 gene) is the sole RNA of its type (4, 5). The box C/D and box H/ACA snoRNPs are found in all eukaryotes and even in Archaea, indicating that these are ancient and highly conserved complexes (6) For a complete listing of all the snoRNA genes in S cerevisiae, see the table of snoRNAs.

Box H/ACA snoRNAs

The box H/ACA snoRNAs typically adopt a conserved secondary structure consisting of two hairpins connected by a hinge region which contains the box H sequence motif; the second hairpin is followed by the sequence motif 'ACA' which is always three nucleotides upstream of the mature 3'-end of the snoRNA (6). Each H/ACA snoRNA associates with a set of conserved proteins: Cbf5p (the pseudouridine synthase catalytic subunit) and Gar1p, Nhp2p, and Nop10p to form a H/ACA type small nucleolar ribonucleoprotein complex, or snoRNP (6).

Most of the box H/ACA snoRNPs pseudouridylate uridine bases within the 18S or 25S rRNAs, but but some target other RNAs such as the U2 snRNA encoded by LSR1 (4, 3). Pseudouridylation, as well as 2'-O-ribose methylation, of the large primary rRNA occurs immediately after transcription and prior to various cleavages to generate the mature 18S, 25S, and 5.8S rRNAs (7). See the tables of Modified Nucleotides in RNAs to view known pseudouridylation sites. The site(s) of pseudouridylation is specified by internal loops, found in one or both of the hairpins, containing a stretch of from 9-13 nucleotides that is complementary to the target RNA and which determines the site of pseudouridylation (6). The purpose of these RNA modifications is not clear, as loss of any particular pseudouridylated site, or the specific snoRNA that directs it, is generally tolerated with no observable phenotype (3). However, it is notable that the sites of modification are in functionally important regions and many are conserved across species (4, 8

The role of snoRNAs in converting the primary rRNA transcript into mature rRNAs

While most of the snoRNAs are not essential and are involved in RNA modification, either 2'-O-ribose methylation or pseudouridylation, a few, including members of each of the three families, are required for endonucleolytic cleavage steps in the processing to convert the primary rRNA transcript into the mature 18S, 5.8S, and 25S rRNA molecules (4, 7). Two box C/D snoRNAs, U3 (produced by two genes SNR17A and SNR17B) and U14 (produced by SNR128) and two box H/ACA snoRNPs, snR30 and snR10 are required for cleavage of the primary rRNA transcript. Depletion of U3, U14, or snR30 results in depletion of the 18S rRNA and complete lack of any one of these snoRNAs is lethal (4, 7). The snR10 snoRNA is not essential and its deletion produces only a mild reduction in 18S rRNA accumulation (7). U14 and snR10 are involved in both endonucleolytic cleavage steps and in targeting RNA modification reactions (7). In addition, RNase MRP is involved in endonucleolytic cleavage to produce the mature 5.8S rRNA molecule; its depletion produces lessened accumulation of the 5.8S rRNA. However, while RNase MRP is essential, it is not essential for rRNA processing as there is an alternative minor processing pathway (7).

The genomic organization of snoRNAs

The genomic organization of the box C/D snoRNAs in S. cerevisiae is notable in that it is quite variable. Some of these genes are encoded within the introns of protein coding genes, as is the case for vertebrate snoRNAs. Other snoRNA genes are found in polycistronic arrays, containing from two to seven snoRNA genes, a common organization for plant snoRNAs. Additionally, S. cerevisiae also has independently transcribed monocistronic box C/D snoRNA genes (9). The genomic organization of the box H/ACA snoRNAs is not as variable as that of the box C/D snoRNAs, and none are found within polycistronic transcripts. Almost all of them are monocistronic genes, though a couple are found within the introns of protein coding genes (4). In addition, while almost all of the snoRNA genes in S. cerevisiae are transcribed by RNA polymerase II, snR52 is transcribed by RNA polymerase III (10).

Last updated: 2007-06-29