The 3′UTR of human MAVS mRNA contains multiple regulatory elements for the control of protein expression and subcellular localization

Post-transcriptional regulation controls the mRNA stability, translation efficiency, and subcellular localization of a protein. The mitochondrial antiviral signaling protein (MAVS) plays a vital role in innate antiviral immunity. The MAVS mRNA has a long 3' untranslated region (UTR, > 9 kb) and an understanding of this region may help to explain the post-transcriptional regulation in a key protein. In this study, we aimed to characterize the role of the MAVS 3'UTR during MAVS expression by truncating the 3'UTR into different fragments so as to identify the regulatory elements. We found that the different fragments (H1-H5) of the MAVS 3'UTR play different roles in regulating the subcellular localization and function of MAVS. Three AU-rich elements (AREs) in the MAVS 3'UTR H1 fragment (region 1-3445 in the 3'UTR) repressed MAVS expression by interacting with HuR to destabilize its mRNA. The MAVS 3'UTR H5 fragment (region 5955-7687 in the 3'UTR) affected the cellular localization of MAVS in mitochondria and influenced the subsequent antiviral function. Four miR-27a binding sites were recognized in the MAVS 3'UTR, and treatment of miR-27a inhibited MAVS expression and promoted the replication of the vesicular stomatitis virus (VSV). The identification of multiple regulatory elements in the MAVS 3'UTR offers new insights into the precise control of MAVS expression in innate immunity.