Monday, March 13 2023, 4pm C127 Davison Life Sciences My work focuses on the molecular pathways that allow cells to measure and respond to changes in their metabolic environment. The biochemical bases of how any given change is sensed and subsequently communicated to coordinate complex decisions are sparsely understood. A particular interest is the underexplored role that RNAs can play in this communication. Like proteins, RNAs can selectively bind small molecules, and these interactions can modulate the RNA’s function through a variety of molecular mechanisms. Yet, examples of this phenomenon remain almost entirely restricted to a small number of examples in bacteria despite the underlying principle—that diverse RNA sequences and structures can bind small molecules with exquisite selectivity and affinity—being universal. My talk will outline two complementary, high-throughput experimental methods developed to query the RNA-metabolite interactome: an equilibrium dialysis and mass spectrometry platform to simultaneously measure interactions between purified RNAs of interest and 450 metabolites, and a high-throughput structure probing assay to find which RNAs in a complex mixture of thousands (e.g., poly(A)+ RNAs) exhibit changes in structure—as to indicate a binding event—when incubated with a metabolite library. It will cover the biochemical and molecular interrogation of several examples of RNA-metabolite interactions, including a human mRNA whose translational efficiency is regulated by an interaction between its 5′UTR and cyclic AMP, and the identification of ligands for several long-standing “orphan” bacterial riboswitches that suggest direct communication between seemingly disparate metabolic pathways. - Dr. Morgan's abstract Dr. Jeff Morgan University of Utah
