Longley D B, Steel D M, Whitehead A S
Department of Genetics, Trinity College, Dublin, Ireland.
J Immunol. 1999 Oct 15;163(8):4537-45.
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-1beta 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.
人类急性期血清淀粉样蛋白A（A-SAA）是一种主要的急性期反应物，作为机体对炎症的早期反应的一部分，其浓度会急剧增加。A-SAA是由两个几乎相同的基因SAA1和SAA2产生的，这两个基因由促炎细胞因子IL-1和IL-6诱导。在本研究中，我们研究了SAA2 mRNA的5'非翻译区（UTR）和3'非翻译区在调节A-SAA2表达中所起的作用。携带SAA2 5'-UTR和/或3'-UTR的SAA2启动子驱动的荧光素酶报告基因构建体被瞬时转染到HepG2人肝癌细胞系中。在用IL-1β和IL-6诱导嵌合mRNA后，SAA2的5'-UTR和3'-UTR都能够在转录后修饰荧光素酶报告基因的表达。SAA2的5'-UTR促进嵌合荧光素酶转录本的有效翻译，而SAA2的3'-UTR也具有此特性，并且还显著加速报告基因mRNA的降解。我们的数据强烈表明，SAA2的5'-UTR和3'-UTR在A-SAA2蛋白合成的转录后调控中各自发挥着重要的独立作用。
