Abstract 3203: The tri-snRNP spliceosome complex is required for MYC-dependent cancer growth

Spliceosome coordinated RNA splicing is an essential cellular process that can generate an immensely diverse repertoire of RNA. While cancer cells have been known to hijack this process to generate splice forms with oncogenic function, the specific role of spliceosome components in this process is not well understood. In this study, we use an integrative genomic approach to identify PRPF6, a member of the tri-snRNP spliceosome complex as essential for colon cancer growth. We show that, in addition to PRPF6, other tri-snRNP components are coordinately overexpressed or amplified in cancer cells. Inhibition of the tri-snRNP complex, but not other spliceosome components, abrogated cancer cell growth only in dependent cancer cell lines in vitro and in vivo. High resolution transcriptome analysis reveals that the tri-snRNP complex binds and regulates the splicing of a relatively small number of genes, many of which are transcriptional targets of the c-MYC oncogene. Intriguingly, many components of the tri-snRNP complex are mutated in a genetic form of Retinitis Pigmentosa. This genetic corollary suggests that the tri-snRNP complex is necessary in specific cellular contexts that may depend on the proper transcription and splicing of a tri-snRNP regulated set of genes. Citation Format: Adam Adler, Zhaoshi Jiang, Mark McCleland, Elizabeth Blackwood, Sharon Yee, Benjamin Haley, Jean-Philippe Stephan, Sofia Hussain, Vivek Chopra, Ron Firestein. The tri-snRNP spliceosome complex is required for MYC-dependent cancer growth. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3203. doi:10.1158/1538-7445.AM2013-3203 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.