Molecular Cell & Developmental Biology
225 Sinsheimer Laboratories
Phone: 831.459.4986
Fax: 831.459.3139
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Structure and Functional Analysis of Spliceosomes
My lab uses the tools of structural biology to understand how cellular machines carry out their biochemical functions.  Our current focus is the spliceosome, a large protein/RNA complex responsible for editing the information contained in the RNA transcripts of over 90% of human genes.  The spliceosome excises long non-coding intervening sequences (introns) from emerging gene transcripts and then ligates the coding sequences (exons) together.  This process, called splicing, creates messenger RNAs that correctly encode for proteins. The spliceosome is dynamically assembled on every intron from 5 structural RNAs and on the order of 100 different proteins.  We know relatively little about the structures of spliceosome and its components.  Visualizing the architecture of any machine frequently provides insight the mechanisms of its function.  Our goal is to understand how the spliceosome is assembled and how it catalyzes the splicing reaction.

The large size and complexity of many macromolecules provides several challenges to structure determination. With the spliceosome, the task is even more formidable due to its dynamic assembly and likely flexibility.  Therefore, we are meeting these challenges by combining structural and biochemical techniques to study the spliceosome including cryo-electron microscopy (cryo-EM) and X-ray crystallography.  With cryo-EM we directly image complexes preserved at liquid nitrogen temperature.  This technique is suited to large macromolecules available in limited quantities, and with image processing gives an overall shape of the spliceosome.  We use X-ray crystallography to determine atomic-resolution structures of individual spliceosome components.  In addition to these structural studies, we use biochemistry techniques to monitor the changes in proteins and RNA interactions in the spliceosome as the splicing progresses.  As we solve more structures of the spliceosome and its components we will be able to combine our biochemical studies to create highly detailed 3D models of the spliceosome.  These models will be critical in furthering our understanding of the mechanistic underpinnings of splicing and its role in gene editing.

Selected Publications
Tange TO, Shibuya T, Jurica MS, Moore MJ. Biochemical analysis of the EJC reveals two new factors and a stable tetrameric protein core. RNA. Vol 11 (12):1869-83. (2005)

Jurica MS, Sousa D, Moore MJ, Grigorieff N.  Three-dimensional structure of C complex spliceosomes by electron microscopy.  Nat Struct Mol Biol. Vol 11 (3): 265-9. (2004)

Jurica, M.S., Licklider, L.J., Gygi, S.P., Grigorieff, N., Moore, M.J. Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. RNA 8: 426-439 (2002).

Jurica M.S., Moore M.J., Pre-mRNA splicing: awash in a sea of proteins. Mol Cell. 12: 5-14 (2003).

Jurica, M.S., Moore, M.J., Capturing splicing complexes to study structure and mechanism. Methods 28: 336-345 (2002).