Project 466656

Messenger RNA (mRNA) is a molecule that carries DNA-encoded information outside of the nucleus to be translated into proteins. Polyadenylation is an mRNA maturation process that involves the addition of a poly(A) tail after a polyadenylation signal (PAS) located in the 3-untranslated region (3-UTR) of pre-mRNAs. Alternative polyadenylation (APA) is the production of varying 3'-UTR isoforms of an mRNA using distinct PAS in pre-mRNAs. Studies show that cancer cells use shorter 3-UTR APA isoforms. Several authors predict that this global shortening of 3-UTRs contributes to cancer development, a theory that is challenged by the fact that 3-UTR shortening also occurs in healthy proliferative cells through APA. This raises the question of whether 3UTR shortening is a cause or an adaptive response in cancer. I will study this question through Phosphatase and TENsin homolog (PTEN), a well-known tumor suppressor. PTEN is a protein that opposes the phosphoinositide 3-kinase (PI3K) and thus negatively regulates the cancer inducing PI3K/Protein kinase B (Akt) signaling pathway. The goal of my project is to further understand the role of PTEN and global APA on the PI3K/Akt pathway and on cellular health. My hypothesis is that the shortening of PTEN and global mRNAs will increase PI3K/Akt signaling and oncogenic functions. The first objective of my project is to see the precise impact of individual PTEN 3UTR APA isoforms on the PI3K/Akt pathway and on cell health. The second objective of my project is to test the functional impact of global 3UTR shortening on the PI3K/Akt pathway and on cell health. My results will shed light on the impact of PTEN APA on PTEN function and help better understand cancers in which 3-UTR shortening is observed.