The WRAP53α gene undergoes both transcriptional and posttranscriptional regulation in response to DNA damage

Abstract

The Wrap53α mRNA transcript regulates expression of the p53 tumor suppressor gene by binding to the 5'untranslated region of the p53 mRNA transcript. The binding of Wrap53α mRNA, which we demonstrate here is induced in response to a variety of DNA damaging agents, stimulates translation of the p53 mRNA, which increases the levels of active p53 protein in the cell. This allows the cell to respond to DNA damage through a p53-mediated cell cycle arrest or apoptosis. In order to determine whether the Wrap53α gene is regulated at the transcriptional and/or post-transcriptional level we carried out two sets of experiments. In one, we cloned a region of the Wrap53α gene predicted to carry the promoter and transcriptional regulatory elements of Wrap53α and tested for alterations in its activity. In addition, we carried out a series of experiments designed to measure the stability of the Wrap53α mRNA. Our results indicate that while there is a clear transcriptional response to treatment of cells with agents that damage DNA, some treatments also give rise to a post-transcriptional response leading to changes in mRNA stability. © 2018 David Reisman. Hosting by Science Repository. All rights reserved.