Architecture and Reactivity of RNA

Wednesday, October 31, 2007 - 2:05pm - 2:20pm
EE/CS 3-180
Eric Westhof (Université de Strasbourg I (Louis Pasteur))
RNA architecture results from the hierarchical assembly of preformed double-stranded helices defined by Watson-Crick base pairs and RNA modules maintained by non-Watson-Crick base pairs. Surprisingly, the most common RNA-RNA interaction motif, the A-minor motif, is also the least specific in its local requirements. A-minor motifs are mediated by adenines binding into the shallow/minor groove of any combination of stacked and helical Watson-Crick base pairs. Thus, A-minor motifs are mutationally robust and can accommodate many combinations of neutral mutations. This complicates the search of functional RNAs in genomes and dilutes the links between RNA structure and evolution.

The bacterial ribosomal decoding A site exploits this lack of local atomic specificity. There, the adenines A1492 and A1493 of the A site are seen either tucked in within the internal loop or bulging out and poised for interaction. This dynamic equilibrium contributes to the decoding process during recognition of the codon:anticodon Watson-Crick base pairings.

In contrast, for RNA folding, where specificity is a requirement, global, positional and orientational, constraints on the native fold must occur upstream in the folding process. Critical parameters are the lengths of the helices, the co-axiality of the helical stacks, and the structure adopted at the junctions of helices. The molecular neutrality present in the local interactions is thus partially compensated by these global topological criteria, much less accessible to sequence analysis since they are attached to the three-dimensional architecture. The search for functional RNAs in genomes is thereby complexified through this dilution of the direct links between sequences and structures. The simultaneous treatment of 3D structures, structural alignments, and annotations of the interactions should allow hopefully to derive some rules of molecular evolution in structured RNAs.

Lescoute, A. and Westhof, E. (2006) The interaction networks of structured RNAs. Nucleic Acids Res 34, 6587.
Hammann, C. and Westhof, E. (2007) Searching genomes for ribozymes and riboswitches. Genome Biology 8, 210.