Penn Medicine Basic and Translational Research
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Alternate RNA Splicing

The lab of Kristin Lynch, PhD, associate professor of Biochemistry and Biophysics, has developed new types of assays to study alternative splicing in T cells and has devised new models for how splicing is controlled and regulated through cell signaling pathways.  The work offers insights into this highly complex and important process that, until fairly recently, was completely unknown.

One of the most significant recent results of these efforts concerns the immune cell gene CD45.  It encodes several different forms of protein that control important parts of the immune system, including aiding the function of T cells and preventing the immune system from turning against itself. 

Lynch discovered and identified the entire signaling pathway that CD45 uses to transcribe itself into five different forms during the alternative splicing process. Different pieces of the gene (exons) are cut out and the remaining sections joined together to form the mRNA strand.  

The identification of GSK3 and TRAP150 as key players in the workings of CD45 is a major insight into the ways in which alternative splicing can enable multiple proteins to be encoded from a single gene. Such knowledge is critical for the understanding of autoimmune disorders and neurological diseases.  

In general, says Lynch, "an understanding of the patterns and mechanisms of alternative splicing is essential for a full comprehension how the genome is interpreted under different conditions to affect protein function."