Professor of MCD Biology
B.S., Montana State University
Ph.D., University of Washington/FHCRC
Postdoctorate, Brandeis University
Structural and Functional Analysis of Spliceosomes
My lab uses the tools of structural biology and biochemistry to investigate the cellular machinery responsible for editing the information contained in the RNA transcripts of nearly all of human genes. This machinery, called the spliceosome, splices out intron sequences that interrupt gene transcripts and joins exon sequences to make messenger RNAs that correctly encode for proteins. The goal of our research is to understand how the spliceosome is assembled and how it catalyzes the splicing reaction, but this is hampered by how relatively little we know about the spliceosome's architecture. The spliceosome presents special challenges to structure determination. It is assembled from many parts including 5 structural RNAs and on the order of 100 different proteins. Additionally, the spliceosome is a dynamic machine, cycling through many short-lived conformations during the splicing process.
Our research group is meeting these challenges by combining structural and biochemical techniques to study the spliceosome. For example, we use electron microscopy to directly image very limited amounts of splicing complexes that we can isolate. We employ image processing procedures that, in combination with labeling studies, we use to develop 3D models of the spliceosome. In parallel, we use a variety of biochemical methods, including mass spectrometry and high throughput screening, to capture and characterize different spliceosome conformations and to study individual complex components. As we continue to further our biochemical and structural understanding of the spliceosome, we will generate increasingly detailed models of this important cellular machine that will finally shed a light on the mechanistic underpinnings of splicing.
Please follow this link to find the lab's publications in the National Library of Medicine's PubMed database.
Localization of pre-mRNA exons within the C-complex spliceosome by cryo-electron microscopy. For details, see Alcid and Jurica (2008) Nat Struct Mol Biol. 15:213-5.