The Keane lab will explore how the structural configurations of large RNAs control the production of smaller regulatory RNA molecules. The full sequencing of the human genome revealed the surprising existence of a vast assortment of small RNA molecules that have the ability to regulate the activity of genes. Among these regulatory RNAs, microRNAs play critical roles in the control of gene expression. These microRNAs are encoded in larger RNA transcripts that must be trimmed to produce the active regulatory molecules. To complicate things further, some precursor transcripts contain an array of different microRNAs that must be generated independently, as they are often present in different quantities in the cell. Using techniques in molecular and structural biology combined with a method I developed for monitoring the structure of large RNA molecules, my lab will elucidate the conformational “switch” that directs the processing of microRNAs encoded on large primary transcripts. We will also identify proteins that specifically interact with and alter the structure of the large primary microRNA, differentially altering access to the enzymes that process and release its individual microRNAs. Because many of the microRNA targets we are studying are enriched in various cancers, our work could lead to novel forms of chemotherapy.