Simbios Talk by Eric Westhof,Université Louis Pasteur, France, June 1, 2007

Title: Non-Watson-Crick Base Pairs, RNA Motifs & RNA Networks

RNA architecture is now visualized as the hierarchical assembly of preformed double-stranded helices defined by Watson-Crick base pairs and RNA modules maintained by non-Watson-Crick base pairs. All base-base pairwise interactions present in nucleic acids have been classified in twelve families where each family is a 4x4 matrix of the bases A, G, C, U. This classification allows to deduce the isotericity matrices which yield all the possible and geometrically equivalent base pairs in a given family. These isostericity matrices have been verified for several RNA motifs using structural alignments anchored by crystallographic structures. Various recurrent motifs have been analyzed along such lines. Surprisingly, the most common RNA-RNA interaction motif, the A-minor motif, is also the least specific in its requirements. Thus, key constraints on the native fold 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. Three-way junctions with two helices approximately co-axially stacked can be divided into three main families depending on the relative lengths of the segments linking the three Watson-Crick helices. Each family has topological characteristics with some conservation in the non-Watson-Crick pairs within the linking segments as well as in the types of contacts between the segments and the helices. The most populated family presents tertiary interactions between two helices as well as extensive shallow/minor groove contacts between a linking segment and the third helix. The links to the search of functional RNAs in genomes and to the relationships between RNA structure and RNA evolution will be discussed.

Lescoute, A. and Westhof, E. (2006) Topology of three-way junctions in folded RNAs. RNA 12, 83-93.

Lescoute, A. and Westhof, E. (2006) The interaction networks of structured RNAs. Nucleic Acids Res 34, 6587-6604.