RNA plays a critical role in mediating every step of the cellular information transfer pathway from DNA-encoded genes to functional proteins. Its diversity of biological functions stems from the ability of RNA to act as a carrier of genetic information and to adopt complex three-dimensional folds that create sites for chemical catalysis. Atomicresolution structures of several large RNA molecules, determined by X-ray crystallography, have elucidated some of the means by which a global fold is achieved. Within these RNAs are tertiary structural motifs that enable the highly anionic double-stranded helices to tightly pack together to create a globular architecture. In this article we present an overview of the structures of these motifs and their contribution to the organization of large, biologically active RNAs. Base stacking, participation of the ribose 2'-hydroxyl groups in hydrogen-bonding interactions, binding of divalent metal cations, noncanonical base pairing, and backbone topology all serve to stabilize the global structure of RNA and play critical roles in guiding the folding process. Studies of the RNA-folding problem, which is conceptually analogous to the protein-folding problem, have demonstrated that folding primarily proceeds through a hierarchical pathway in which domains assemble sequentially. Formation of the proper tertiary interactions between these domains leads to discrete intermediates along this pathway. Advances in the understanding of RNA structure have facilitated improvements in the techniques that are utilized in modeling the global architecture of biologically interesting RNAs that have been resistant to atomic-resolution structural analysis.

Reference: Batey RT, Rambo RP, Tertiary Motifs, Doudna JA. (1999). Tertiary Motifs in RNA Structure and Folding. Angew Chem Int Ed Engl. Aug; 38(16):2326-2343.

The paper is available at http://rna.berkeley.edu/Publications/angchem-38-2327.pdf