Posttranscriptional regulation of acute phase serum amyloid A2 expression by the 5 '- and 3 '-untranslated regions of its mRNA

Human acute-phase serum amyloid A protein (A-SAA) is a major acute phase re actant, the concentration of which increases dramatically as part of the bo dy's early response to inflammation. A-SAA is the product of two almost ide ntical genes, SAA1 and SAA2, which are induced by the pro-inflammatory cyto kines, 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 e xpression. SAA2 promoter-driven luciferase reporter gene constructs carryin g the SAA2 5'-UTR and/or 3'-UTR were transiently transfected into the HepG2 human hepatoma cell line. After induction of chimeric mRNA with LL-1 beta 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 S AA2 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 posttranscriptio nal regulation of A-SAA2 protein synthesis.