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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011397-01
Application #
8349520
Study Section
Project Start
Project End
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Budget End
Support Year
1
Fiscal Year
2011
Total Cost
$176,740
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
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