Through a RNAi synthetic lethal screen we have identified a number of key mRNA splicing factors to be required for the viability of Ras mutant cancer cells. PURPOSE In this project we aim to address the following questions: 1. the mechanism by which a subset of mRNA splicing factors is synthetically lethal with Ras mutation;2. which cellular proteins are differentially spliced in Ras mutant cells;3. How the changes in mRNA splicing pattern in these cells affect their function in the context of Ras mutation SIGNIFICANT MATERIALS AND METHODS 1. shRNAs that target a selected number of splicing factors. 3. RNA-seq protocol for quantifying mRNA splicing pattern changes FY2011 ACCOMPLISHMENT We have validated shRNAs that target a number mRNA splicing factors that are identified to be synthetically lethal with KRAS. We have generated cell lines stably expressing rescue cDNAs to these factors. We are carrying RNA-seq experiments to characterize mRNA splicing patters in KRAS WT and mutant cells and with or without splicing factor knockdown.