Small Nucleolar RNAs (snoRNAs) from the Yeast Saccharomyces cerevisiae:

A comprehensive database of
S. cerevisiae H/ACA and C/D box snoRNAs.
VERSION 2.0

Brief history of the database:

This is an upgraded and enhanced version of a database established by Dimtry A. Samarsky and reported in 1999; click here for the PubMed listing. Stylistic elements and arrangement of the interface for the updated yeast snoRNA database were fashioned after the very effective format used for the human database, snoRNABase, at the Laboratoire de Biologie Moléculaire Eucaryote (LBME) in Toulouse, France; click here for the PubMed listing.
A manuscript describing the current version has been published.

Overview of the small nucleolar RNAs (snoRNAs)

The small nucleolar RNAs (snoRNAs) are stable RNA components in nucleolar ribonucleoprotein complexes called snoRNPs ('snorps'). The snoRNPs function in the post-transcriptional modification of ribosomal and other RNAs, and in cleavage of precursor rRNAs. Based on these functions snoRNPs are often referred to as 'modifying' or 'processing' snoRNPs. Two types of modifications are created by snoRNPs, 2'-O-methylation (Nm) and isomerization of uridine to pseudouridine (Ψ). In both the modification and cleavage processes the snoRNP complex interacts directly with the RNA substrate through complementary sequences in the snoRNA. Catalysis of the modification reactions is mediated by a core snoRNP protein. For reviews on snoRNAs see (1-5).
 
The snoRNAs are believed to be ubiquitous among eukaryotes and have been documented in a wide variety of organisms, including protists, fungi, flies, plants and vertebrates (6-17). The total number of unique snoRNAs has been demonstrated to be upwards of 80 species in the yeast S. cerevisiae and more than 300 in human (18). Vertebrates contain closely related small RNAs in the Cajal bodies (scaRNAs) and the corresponding RNPs (scaRNPs) are known to function in nucleotide modification of spliceosomal snRNAs transcribed by RNA Pol II. Archaeal organisms have related RNAs and RNPs (19-22). The population of snoRNAs in the yeast S. cerevisiae is the best characterized thus far.

Schematic of MRP

The snoRNAs are grouped into three classes based on conserved structural elements, and the corresponding snoRNPs contain core proteins that are also class-specific (2, 3, 23). All snoRNPs in a family contain the same core proteins and in nearly all cases the snoRNA component is the main feature that distinguishes the biogenesis, structure, and function of each snoRNP (24-31). One class of snoRNAs has only one member per organism, the MRP RNA (Figure 1a), while the other two classes are composed of large families of snoRNAs. A small number of snoRNPs in each class, including the MRP species, participate in key cleavages of precursor rRNA transcribed from the large, polycistronic rDNA operon. However, the vast majority of snoRNPs create modified nucleotides in ribosomal RNA and (thus far in yeast) the U2 spliceosomal snRNA.
 

Schematic of C/D Box Family

The snoRNAs in one large family are defined by short sequence elements termed boxes C and D, and these snoRNAs frequently contain a second set of related elements called boxes C' and D'. Most C/D snoRNPs create 2'-O-methylatated nucleotides (Nm). The methylating snoRNPs are directed to a target site in a substrate, through base pairing of a long (10-20 nucleotide) guide sequence in the snoRNA that is complementary to the sequence to be modified. This class of guide snoRNAs can contain one or two guide sequences located upstream of box D and/or box D'. Base pairing with the substrate encompasses the target nucleotide, and methylation takes place at a site located five nucleotides upstream from box D/D' on the opposing substrate strand (Figure 1b) (3). The snoRNAs are often referred to as 'single-' and 'double-guide' snoRNAs, which are able to direct methylation to one or two sites, and some cases to additional sites.
 

Schematic of H/ACA Box Family

The other large family of snoRNAs is defined by elements called boxes H and ACA, and most of these snoRNAs guide conversion of uridine to pseudouridine (Ψ) at specific sites in the substrate RNA (Figure 1c) (2, 5, 23). Site selection here involves base pairing of two short guide sequences in the snoRNA with complementary sequences that flank the substrate uridine to be isomerized. The two short sequences composing the guide are each 3-10 nts and the sequences occur in the bulge region of a guide domain consisting of a stem-bulge-stem-loop; the bulge region is referred to as the 'pseudouridylation pocket'. The Ψ guide snoRNAs in S. cerevisiae have one or two guide domains and are able to target one, two or (currently) up to 4 uridines in a substrate RNA.
 
Crystal structure of an H/ACA box RNP
from Pyrococcus furiosus (Li and Ye, 2006)
(PDB CODE: 2HVY)
Cbf5p   Gar1   Nop10   L7AE   RNA

References:
 
1. Bachellerie, J. P., J. Cavaille, and A. Huttenhofer. 2002. The expanding snoRNA world. Biochimie 84:775-790.
2. Meier, U. T. 2005. The many facets of H/ACA ribonucleoproteins. Chromosoma 114:1-14.
3. Bertrand, E., and M. J. Fournier. 2004. The snoRNPs and Related Machines: Ancient Devices That Mediate Maturation of rRNA and Other RNAs, p. 223-257. In M. O. J. Olson (ed.), The Nucleolus. Eurekah.com and Kluwer Academic / Plenum Publishers, Georgetown, TX; New York, NY.
4. Henras, A. K., C. Dez, and Y. Henry. 2004. RNA structure and function in C/D and H/ACA s(no)RNPs. Curr. Opin. Struct. Biol. 14:335-343.
5. Meier, U. T. 2006. How a single protein complex accommodates many different H/ACA RNAs. Trends Biochem. Sci. 31:311-315.
6. Schattner, P., W. A. Decatur, C. A. Davis, M. Ares, Jr., M. J. Fournier, and T. M. Lowe. 2004. Genome-wide searching for pseudouridylation guide snoRNAs: analysis of the Saccharomyces cerevisiae genome. Nucleic Acids Res. 32:4281-4296.
7. Torchet, C., G. Badis, F. Devaux, G. Costanzo, M. Werner, and A. Jacquier. 2005. The complete set of H/ACA snoRNAs that guide rRNA pseudouridylations in Saccharomyces cerevisiae. RNA 11:928-938.
8. Russell, A. G., M. N. Schnare, and M. W. Gray. 2006. A large collection of compact box C/D snoRNAs and their isoforms in Euglena gracilis: structural, functional and evolutionary insights. J. Mol. Biol. 357:1548-1565.
9. Russell, A. G., M. N. Schnare, and M. W. Gray. 2004. Pseudouridine-guide RNAs and other Cbf5p-associated RNAs in Euglena gracilis. RNA 10:1034-1046.
10. Li, S. G., H. Zhou, Y. P. Luo, P. Zhang, and L. H. Qu. 2005. Identification and functional analysis of 20 Box H/ACA small nucleolar RNAs (snoRNAs) from Schizosaccharomyces pombe. J. Biol. Chem. 280:16446-16455.
11. Tycowski, K. T., and J. A. Steitz. 2001. Non-coding snoRNA host genes in Drosophila: expression strategies for modification guide snoRNAs. Eur. J. Cell Biol. 80:119-125.
12. Huang, Z. P., H. Zhou, H. L. He, C. L. Chen, D. Liang, and L. H. Qu. 2005. Genome-wide analyses of two families of snoRNA genes from Drosophila melanogaster, demonstrating the extensive utilization of introns for coding of snoRNAs. RNA 11:1303-1316.
13. Chen, C. L., D. Liang, H. Zhou, M. Zhuo, Y. Q. Chen, and L. H. Qu. 2003. The high diversity of snoRNAs in plants: identification and comparative study of 120 snoRNA genes from Oryza sativa. Nucleic Acids Res. 31:2601-2613.
14. Brown, J. W., M. Echeverria, L. H. Qu, T. M. Lowe, J. P. Bachellerie, A. Huttenhofer, J. P. Kastenmayer, P. J. Green, P. Shaw, and D. F. Marshall. 2003. Plant snoRNA database. Nucleic Acids Res. 31:432-435.
15. Cao, X., G. Yeo, A. R. Muotri, T. Kuwabara, and F. H. Gage. 2006. Noncoding RNAs in the mammalian central nervous system. Annu. Rev. Neurosci. 29:77-103.
16. Huttenhofer, A., M. Kiefmann, S. Meier-Ewert, J. O'Brien, H. Lehrach, J. P. Bachellerie, and J. Brosius. 2001. RNomics: an experimental approach that identifies 201 candidates for novel, small, non-messenger RNAs in mouse. EMBO J. 20:2943-2953.
17. Uliel, S., X. H. Liang, R. Unger, and S. Michaeli. 2004. Small nucleolar RNAs that guide modification in trypanosomatids: repertoire, targets, genome organisation, and unique functions. Int. J. Parasitol. 34:445-454.
18. Lestrade, L., and M. J. Weber. 2006. snoRNA-LBME-db, a comprehensive database of human H/ACA and C/D box snoRNAs. Nucleic Acids Res. 34:D158-162.
19. Omer, A. D., S. Ziesche, W. A. Decatur, M. J. Fournier, and P. P. Dennis. 2003. RNA-modifying machines in archaea. Mol. Microbiol. 48:617-629.
20. Gaspin, C., J. Cavaille, G. Erauso, and J. P. Bachellerie. 2000. Archaeal homologs of eukaryotic methylation guide small nucleolar RNAs: lessons from the Pyrococcus genomes. J. Mol. Biol. 297:895-906.
21. Dennis, P. P., and A. Omer. 2005. Small non-coding RNAs in Archaea. Curr. Opin. Microbiol. 8:685-694.
22. Zago, M. A., P. P. Dennis, and A. D. Omer. 2005. The expanding world of small RNAs in the hyperthermophilic archaeon Sulfolobus solfataricus. Mol. Microbiol. 55:1812-1828.
23. Yu, Y.-T., R. M. Terns, and M. P. Terns. 2005. Mechanisms and functions of RNA-guided RNA modification. In H. Grosjean (ed.), Fine-Tuning of RNA Modifications by Modification and Editing, vol. 12. Springer, Goteborg.
24. Kufel, J., C. Allmang, L. Verdone, J. Beggs, and D. Tollervey. 2003. A complex pathway for 3' processing of the yeast U3 snoRNA. Nucleic Acids Res. 31:6788-6797.
25. LaCava, J., J. Houseley, C. Saveanu, E. Petfalski, E. Thompson, A. Jacquier, and D. Tollervey. 2005. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121:713-724.
26. Ghazal, G., D. Ge, J. Gervais-Bird, J. Gagnon, and S. Abou Elela. 2005. Genome-wide prediction and analysis of yeast RNase III-dependent snoRNA processing signals. Mol. Cell. Biol. 25:2981-2994.
27. Ballarino, M., M. Morlando, F. Pagano, A. Fatica, and I. Bozzoni. 2005. The cotranscriptional assembly of snoRNPs controls the biosynthesis of H/ACA snoRNAs in Saccharomyces cerevisiae. Mol. Cell. Biol. 25:5396-5403.
28. Morlando, M., M. Ballarino, P. Greco, E. Caffarelli, B. Dichtl, and I. Bozzoni. 2004. Coupling between snoRNP assembly and 3' processing controls box C/D snoRNA biosynthesis in yeast. EMBO J. 23:2392-2401.
29. Watkins, N. J., I. Lemm, D. Ingelfinger, C. Schneider, M. Hossbach, H. Urlaub, and R. Luhrmann. 2004. Assembly and maturation of the U3 snoRNP in the nucleoplasm in a large dynamic multiprotein complex. Mol. Cell 16:789-798.
30. Houalla, R., F. Devaux, A. Fatica, J. Kufel, D. Barrass, C. Torchet, and D. Tollervey. 2006. Microarray detection of novel nuclear RNA substrates for the exosome. Yeast 23:439-454.
31. Richard, P., and T. Kiss. 2006. Integrating snoRNP assembly with mRNA biogenesis. EMBO Rep. 7:590-592.
Last update: February 19, 2009 3:35 PM.