Deciphering the Mechanism of Alternative Cleavage and Polyadenylation in Mantle Cell Lymphoma (MCL)

: Until recently, 3 end formation was believed to be a static event. The discovery that transformed and rapidly proliferating cells use alternative cleavage and polyadenylation (APA) to shorten the 3 UTR of their mRNAs has important implications in cancer. Truncation of the cyclin D1 mRNA in mantle cell lymphoma (MCL) is one of the earliest reported cases of APA. However, the mechanism that APA is still unknown. The goal of this project is to identify the mechanism of cyclin D1 APA regulation in cancer. So far we have been able to develop dual luciferase plasmids containing the cyclin D1 3 UTR which will enable us to determine the elements important for APA in MCL. In addition, by using RNA Seq. CFIm25 has been identified as an important global regulator of shortening of cyclin D1 mRNA and other genes. The shortened transcripts have been shown to result in increased protein levels resulting in increased cell proliferation, a hallmark of cancer. These data provides a clear link between CFIm25 and regulation of APA and the utility of using novel RNA Seq. technology. This provides a strong research platform for continued research on this project.