Abstract
The recent deluge of new RNA structures, including complete atomic-resolution views of both subunits of the ribosome, has on the one hand literally overwhelmed our individual abilities to comprehend the diversity of RNA structure, and on the other hand presented us with new opportunities for comprehensive use of RNA sequences for comparative genetic, evolutionary and phylogenetic studies. Two concepts are key to understanding RNA structure: hierarchical organization of global structure and isostericity of local interactions. Global structure changes extremely slowly, as it relies on conserved long-range tertiary interactions. Tertiary RNA–RNA and quaternary RNA–protein interactions are mediated by RNA motifs, defined as recurrent and ordered arrays of non-Watson–Crick base-pairs. A single RNA motif comprises a family of sequences, all of which can fold into the same three-dimensional structure and can mediate the same interaction(s). The chemistry and geometry of base pairing constrain the evolution of motifs in such a way that random mutations that occur within motifs are accepted or rejected insofar as they can mediate a similar ordered array of interactions. The steps involved in the analysis and annotation of RNA motifs in 3D structures are: (a) decomposition of each motif into non-Watson–Crick base-pairs; (b) geometric classification of each basepair; (c) identification of isosteric substitutions for each basepair by comparison to isostericity matrices; (d) alignment of homologous sequences using the isostericity matrices to identify corresponding positions in the crystal structure; (e) acceptance or rejection of the null hypothesis that the motif is conserved.
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Contributor Information
Neocles B. Leontis, Email: Leontis@bgnet.bgsu.edu
Eric Westhof, Email: e.westhof@ibmc.u-strasfg.fr.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ban N., Nissen P., Hansen J., Moore P. B., Steitz T. A. The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. Science. 2000 Aug 11;289(5481):905–920. doi: 10.1126/science.289.5481.905. [DOI] [PubMed] [Google Scholar]
- Bartels H., Gluehmann M., Janell D., Schluenzen F., Tocilj A., Bashan A., Levin I., Hansen H. A., Harms J., Kessler M. Targeting exposed RNA regions in crystals of the small ribosomal subunits at medium resolution. Cell Mol Biol (Noisy-le-grand) 2000 Jul;46(5):871–882. [PubMed] [Google Scholar]
- Batey RT, Rambo RP, Doudna JA. Tertiary Motifs in RNA Structure and Folding. Angew Chem Int Ed Engl. 1999 Aug;38(16):2326–2343. doi: 10.1002/(sici)1521-3773(19990816)38:16<2326::aid-anie2326>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
- Carter A. P., Clemons W. M., Brodersen D. E., Morgan-Warren R. J., Wimberly B. T., Ramakrishnan V. Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature. 2000 Sep 21;407(6802):340–348. doi: 10.1038/35030019. [DOI] [PubMed] [Google Scholar]
- Cech T. R., Damberger S. H., Gutell R. R. Representation of the secondary and tertiary structure of group I introns. Nat Struct Biol. 1994 May;1(5):273–280. doi: 10.1038/nsb0594-273. [DOI] [PubMed] [Google Scholar]
- Correll C. C., Freeborn B., Moore P. B., Steitz T. A. Metals, motifs, and recognition in the crystal structure of a 5S rRNA domain. Cell. 1997 Nov 28;91(5):705–712. doi: 10.1016/s0092-8674(00)80457-2. [DOI] [PubMed] [Google Scholar]
- Harms J., Schluenzen F., Zarivach R., Bashan A., Gat S., Agmon I., Bartels H., Franceschi F., Yonath A. High resolution structure of the large ribosomal subunit from a mesophilic eubacterium. Cell. 2001 Nov 30;107(5):679–688. doi: 10.1016/s0092-8674(01)00546-3. [DOI] [PubMed] [Google Scholar]
- Leontis N. B., Westhof E. Conserved geometrical base-pairing patterns in RNA. Q Rev Biophys. 1998 Nov;31(4):399–455. doi: 10.1017/s0033583599003479. [DOI] [PubMed] [Google Scholar]
- Leontis N. B., Westhof E. Geometric nomenclature and classification of RNA base pairs. RNA. 2001 Apr;7(4):499–512. doi: 10.1017/s1355838201002515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leontis N. B., Westhof E. The 5S rRNA loop E: chemical probing and phylogenetic data versus crystal structure. RNA. 1998 Sep;4(9):1134–1153. doi: 10.1017/s1355838298980566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leontis Neocles B., Stombaugh Jesse, Westhof Eric. The non-Watson-Crick base pairs and their associated isostericity matrices. Nucleic Acids Res. 2002 Aug 15;30(16):3497–3531. doi: 10.1093/nar/gkf481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Michel F., Jacquier A., Dujon B. Comparison of fungal mitochondrial introns reveals extensive homologies in RNA secondary structure. Biochimie. 1982 Oct;64(10):867–881. doi: 10.1016/s0300-9084(82)80349-0. [DOI] [PubMed] [Google Scholar]
- Westhof E. Westhof's rule. Nature. 1992 Aug 6;358(6386):459–460. doi: 10.1038/358459b0. [DOI] [PubMed] [Google Scholar]