APOBEC3A regulates transcription from interferon-stimulated response elements

Abstract

Significance APOBEC3A (A3A) is a DNA binding enzyme that introduces mutations through its cytidine deaminase activity. In addition, A3A can repress proviral HIV-1 and retroelements within the host genome by a deaminase-independent mechanism. Here, we demonstrate that A3A binds to the promoter sequence of interferon (IFN)-stimulated gene (ISG)15 and suppresses IFN-stimulated response element activity. In a deaminase-independent manner, A3A reduces ISG15 expression in response to IFN stimulation. A3A overexpression decreases and A3A knockout increases the expression of several ISGs in response to IFN-α treatment. Since A3A itself is an ISG, our data suggest that A3A plays a role in a negative feedback loop to control ISG expression.