Research Program

In the Rader Lab we seek to develop tools that will allow us to investigate the mechanism of pre-mRNA splicing at the atomic level. We are addressing such questions as: How does the conformation of pre-mRNA change during the course of the splicing reaction? How do small, nuclear RNAs and their associated proteins identify the splice junctions and promote the splicing reaction? And what do these complexes look like in three dimensions?

Fluorescence
We are applying two biophysical methods to address these questions: fluorescence and x-ray crystallography. By incorporating fluorescent dyes into pre-mRNA, we can use Fluorescence Resonant Energy Transfer, or FRET, to precisely measure the distance between the dyes. We will therefore be able to monitor conformational changes within the pre-mRNA as they occur.
X-ray Crystallography
Very little is known about the three-dimensional structure of any of the proteins or RNAs involved in pre-mRNA splicing, let alone the larger splicing complexes. We are expressing and purifying splicing proteins with the aim of determining their structures by x-ray crystallography.
Yeast Genetics and Biochemistry
In order to ground our biochemical observations in biology, we use the tools of yeast genetics. Through a combination of genetic screens, directed genetics, and biochemical assays, we allow the yeast to tell us which interactions or molecular functions are biologically important.
For a UNBC media release on Rader Lab research, click here.
To read a more detailed description of our interests in the activation of the U6 snRNP for splicing, click here.



 

crystal photo copyright NASA