G-quadruplex Mediated Splicing of p53 mRNA

The protein p53 is a master regulator of the cell cycle and its mutation/inactivation is associated with over 50% of cancer cases. Mutations in p53 are associated with worse survival rates, resistance to therapies, and other risk factors in breast cancer specifically. p53 is encoded by the TP53 gene and is expressed as several transcripts. In the G-rich portion of intron 3, secondary DNA structures known as G-quadruplexes are able to form. The stabilization of these G-quadruplexes leads to correct splicing of intron 2, thus making a functional p53 protein. A known quadruplex-stabilizing compound (TMPyP4) was tested to determine its ability to stabilize these structures through electronic circular dichroism. The effect TMPyP4 had on pre-mRNA splicing of p53 in MCF-7 breast cancer cells was also evaluated through real-time quantitative polymerase chain reaction and gel electrophoresis. This compound did possess stabilizing qualities in the intron 3 region of the TP53 gene. Although more pharmacologic testing needs to be completed, TMPyP4 shows potential to regulate splicing of p53, which could improve the prognosis of breast cancer patients