Prof. Robert Batey, University of Colorado Boulder

Riboswitch-mediated regulation of mRNAs

Riboswitches are structured elements found in the 5’-untranslated regions of mRNAs that specifically bind small molecule to regulate gene expression in a cis-fashion. These riboregulatory elements typically contain two domains: an aptamer domain that binds a cellular metabolite and an expression platform that directs expression of the mRNA. We have solved the X-ray crystal structures of the aptamer domains of the purine, two S-adenosylmethionine, and the lysine responsive riboswitches in complex with their cognate ligands, revealing complex tertiary architectures that scaffold the ligand-binding pocket. In each case, almost all of the functional groups of the ligand are directly or indirectly sensed by the RNA resulting in extremely high binding specificity. Complementing these structures, we have used biochemical methods to probe the nature of the unliganded form of the aptamer domains, illuminating aspects of their ligand-dependent folding. These studies reveal that regulation is achieved through a series of ligand-induced tertiary structural changes in the RNA that serve to stabilize a helix that forms part of a secondary structural switch with the expression platform. As genomics are discovering an increasing diversity of non-coding regulatory RNAs, this work provides a mechanistic foundation for how they can achieve functions once solely attributed to proteins.

For more information contact Prof. Yomi Oyelere (404-894-4047).