Natural mRNA Genetic Switches that Bind Metabolites

Yale University, New Haven CT

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Abstract

DESCRIPTION (provided by applicant): Messenger RNAs are typically thought of as passive carriers of genetic information that are acted upon by protein or small RNA-regulatory factors and by ribosomes during the process of translation. Recently, we have found that the 5'-untranslated sequences of numerous prokaryote mRNAs assume a more proactive role in metabolic monitoring and genetic control. The mRNAs serve as metabolite-sensing genetic switches (called "riboswitches") that selectively binding to effector molecules without the need for proteins. The binding event between mRNA and metabolite establishes a distinct RNA structure that, in certain cases is responsible for inhibition of ribosome binding, and in other cases is responsible for inducing transcription termination. These and related findings support our hypothesis that metabolic monitoring through RNA-metabolite interactions is a widespread mechanism of genetic control. We propose to explore the structural and functional characteristics of an FMN-sensing riboswitch with the aim of establishing the basic principles of riboswitch function. These findings will aid in the discovery of new riboswitches and will provide a solid foundation for the generation of designer genetic control elements based on RNA.