Tristetraprolin suppresses AHRR expression through mRNA destabilization

Abstract

The aryl hydrocarbon receptor repressor (AHRR) inhibits the transcription of the aryl hydrocarbon receptor (AHR) by binding to XRE. We report that AHRR expression is inhibited by tristetraprolin (TTP), an AU-rich element (ARE)-binding protein. Overexpression of TTP decreased the mRNA stability and protein expression of AHRR, and TTP-overexpressing cells made smaller colonies than the control. Contrarily, inhibition of TTP by siRNA increased AHRR expression. Analyses of point mutants of the AREs demonstrated that AREs were responsible for the TTP-mediated destabilization of AHRR mRNA. RNA EMSA revealed that TTP directly binds to the AHRR 3'UTR. Taken together, we demonstrate that TTP acts as a negative regulator of AHRR and may affect tumor development through induction of tumor suppressor genes as observed in MDA-MB435.