Non-coding intervening sequences, or introns, interrupt most eukaryotic genes. Cells must remove introns with great precision from these gene transcripts in order to accurately express the genetic information. Intron removal is done through a process called RNA splicing, and the spliceosome is a ribonucleoprotein complex that splices pre-mRNAs through two transesterification reactions. In addition to being highly precise, the spliceosome is also quite flexible; it can splice different sets of expressing sequences, or exons, together to produce multiple splice variants from one gene transcript. Alternative splicing allows human cells to produce a million of proteins from their 50,000 genes. Thus, an abnormal or defective spliceosome would bring disease or even death to an organism. Our goals are to understand the molecular detail of the spliceosome in model organisms as well as to study its function and regulation in normal and cancerous cells.
Project 1: The catalytic core of the spliceosome
Project 2: Yeast Prp2 ATPase and its associated G-patch protein
Project 3: Human DHX16/PRP2 protein in splicing and cell death
Project 4: Finding alternative splicing variants in breast cancer
Experimental Protocol 1: Yeast splicing extracts preparation