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 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.
Longley
D B
DB
Department of Genetics, Trinity College, Dublin, Ireland.
Steel
D M
DM
Whitehead
A S
AS
D020413:3' Untranslated Regions / Q000235:genetics*; D020121:5' Untranslated Regions / Q000235:genetics*; D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000209:Acute-Phase Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C083772:SAA2 protein, human; D000685:Serum Amyloid A Protein; D008156:Luciferases; D001616:beta-Galactosidase