The Department of Biochemistry's weekly BCH 252 seminar series is presented this week by:

Dr. Aaron Hoskins, Associate Professor, Department of Biochemistry, University of Wisconsin-Madison

Seminar Title: "Turning on the Spliceosome"

Abstract:  Spliceosome activation involves dramatic remodeling of the spliceosome in order to create the RNA active site used for pre-mRNA splicing. During this process, the U1 and U4 snRNPs are expelled along with a number of U6, U2, and tri-snRNP specific proteins.  The protein-only Prp19 complex (NTC) is also recruited during these steps to buttress the active site architecture. All of this requires ATP hydrolysis by a number of DExD/H-box, RNA dependent ATPases. We have used colocalization single molecule fluorescence microscopy (CoSMoS) to follow the pathways of spliceosome activation and reveal basic properties of this process. Our work reveals the presence of novel spliceosome activation intermediates which exist transiently (for only a few seconds) and have not yet been observed by cryo-EM or in ensemble assays. Individual protein subcomplexes have unique kinetic and ATP-dependent properties suggestive of distinct functions during activation. Combined our data reveal new insights which can only be obtained by following activation in real time and define the molecular composition of spliceosome complexes for future structural elucidation by cryo-EM.

Faculty Host: Dr. Sean O'Leary, sean.oleary@ucr.edu