Endogenous p53 expression in human and mouse is not regulated by its 3'UTR

Abstract

The TP53 gene encodes the tumor suppressor p53, which is functionally inactivated in many human cancers. Numerous studies found that overexpression of specific microRNAs or RNA-binding proteins can alter p53 expression through binding to cis-regulatory elements in the TP53 3' untranslated region (3'UTR). Although these studies suggested that 3'UTR-mediated p53 expression regulation could play a role in tumorigenesis or could be exploited for therapeutic purposes, they did not investigate post-transcriptional regulation of the native TP53 gene. We used CRISPR/Cas9 to delete the human and mouse p53 3'UTRs while preserving endogenous mRNA processing. This revealed that the endogenous 3'UTR is not involved in regulating p53 mRNA or protein expression neither in steady state nor after genotoxic stress. As we were able to confirm the previously observed repressive effects of the isolated 3'UTR in reporter assays, our data highlight the importance of genetic models in the validation of post-transcriptional gene regulatory effects.