Towards the Visualization of Spliceosomal Intermediates

Type of Award: Catalyst
Date Awarded: February 2016
Award End Date: January 2018
Amount Awarded: $ 200,000.00
PI(s): Yuan He, NU; Joseph Piccirilli, UChicago; Jonathan Staley, UChicago;

Abstract: Our genes are interrupted by nonsense that must be removed during the expression of our genes into proteins, the workhorses of the cell. In gene expression, a gene is first transcribed into a messenger made of RNA, which is similar to DNA. Then, the nonsense is excised and the instructions are spliced together. Lastly, the message is translated to protein. Each step is catalyzed by a macromolecular machine. An understanding of how these machines work requires their visualization at each stage of operation. For over a decade, the transcriptional and translational machinery have been visualized at numerous stages, whereas the first visualization of the splicing machinery has only just been reported. This advance has been enabled by exciting technical breakthroughs in electron microscopy. With our complementary expertise in electron microscopy and splicing machinery, we are uniquely positioned to exploit these breakthroughs to visualize the operation of the splicing machine.