The past two decades of research in RNA catalysis have brought about a remarkable confluence of functional and structural data that, for many RNA enzymes, identify direct catalytic interactions between the ribozyme and its substrates. The more recent x-ray crystallographic structural data are now facilitating a new generation of functional studies: We can now ask how a structured RNA template can be used to position ribozyme and substrate functional groups to achieve extraordinary catalytic rate enhancements. Remarkably, we have shown that the group I ribozyme from Tetrahymena utilizes extensive networks of hydrogen bonding and stacking interactions to link binding specificity to catalytic prowess. These networks even extend to the structural elements peripheral to the catalytic core that are conserved only within a subclass of group I introns. The results of these studies are thus beginning to reveal how functional RNAs, with their limited side chain repertoire and less dense packing, relative to proteins, can nevertheless create and utilize intricate and extensive interaction networks. These properties, revealed in simpler RNA systems, are presumably exploited in the complex multi-step processes driven by functional RNAs such as the ribosome and spliceosome.

Structural networks in RNA catalysis: The new RNA structure-function

243rd National Meeting (2012)

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