<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>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.</p>
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Comp Funct Genomics. 2002 Dec; 3(6):518-524