Posttranscriptional Regulation of Acute Phase Serum Amyloid A2 Expression by the 5′- and 3′-Untranslated Regions of Its mRNA

Abstract

Human acute-phase serum amyloid A protein (A-SAA) is a major acute phase reactant, the concentration of which increases dramatically as part of the body’s early response to inflammation. A-SAA is the product of two almost identical genes, SAA1 and SAA2, which are induced by the pro-inflammatory cytokines, IL-1 and IL-6. In this study, we examine the roles played by the 5′- and 3′-untranslated regions (UTRs) of the SAA2 mRNA in regulating A-SAA2 expression. SAA2 promoter-driven luciferase reporter gene constructs carrying the SAA2 5′-UTR and/or 3′-UTR were transiently transfected into the HepG2 human hepatoma cell line. After induction of chimeric mRNA with IL-1β and IL-6, the SAA2 5′- and 3′-UTRs were both able to posttranscriptionally modify the expression of the luciferase reporter. The SAA2 5′-UTR promotes efficient translation of the chimeric luciferase transcripts, whereas the SAA2 3′-UTR shares this property and also significantly accelerates the rate of reporter mRNA degradation. Our data strongly suggest that the SAA2 5′- and 3′-UTRs each play significant independent roles in the posttranscriptional regulation of A-SAA2 protein synthesis.