Ferré-D'Amaré Lab Research > Gene regulatory RNAs
RNAs play diverse roles in the control of the flow of genetic information and cellular homeostasis. Of particular interest are riboswitches, mRNA domains that directly bind to small molecule metabolites and modulate transcription, translation or splicing. Riboswitches have been discovered in archaea, bacteria and eukarya. We have studied bacterial riboswitches that respond to the intracellular concentration of effectors such as thiamine pyrophosphate (vitamin B1), glucosamine-6-phosphate, preQ1, and c-di-GMP. Because riboswitches control essential metabolic and signaling pathways in pathogenic bacteria, and because these RNAs have evolved the capacity to recognize small molecules with exquisite specificity, they represent attractive targets for the development of novel antibiotics. In addition, they present opportunities for the design of artificial gene-regulatory systems.
• Zhang, J. & Ferré-D'Amaré, A.R. Co-crystal structure of a T-box riboswitch stem I domain in complex with its cognate tRNA. Nature 500, 363-366 (2013) [abstract]
• Zhang, J., Lau, M. & Ferré-D'Amaré, A.R. Ribozymes and riboswitches: modulation of RNA function by small molecules. Biochemistry 49, 9123-9131 (2010). [abstract]
• Klein, D.J., Edwards, T.E. & Ferré-D'Amaré, A.R. Cocrystal structure of a class-I preQ1 riboswitch reveals a pseudoknot recognizing an essential hypermodified nucleobase. Nature Struct. Mol. Biol. 16, 343-344 (2009). [abstract]
• Xiao, H., Edwards, T.E. & Ferré-D'Amaré, A.R. Structural basis for specific, high-affinity tetracycline binding by an in vitro evolved aptamer and artificial riboswitch. Chem. Biol. 15, 1125-1137 (2008). [abstract]
• Edwards, T.E., & Ferré-D’Amaré, A.R. Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate analogs reveal adaptive RNA-small molecule recognition. Structure 14, 1459-1468 (2006). [abstract]