Multiple regions within the promoter of the murine Ifnar-2 gene confer basal and inducible expression.
The (murine) type I interferon (IFN) receptor, muIfnar-2, is expressed ubiquitously, and exists as both transmembrane and soluble forms. In the present study we show that the gene encoding muIfnar-2 spans approx. 33 kb on mouse chromosome 16, and consists of nine exons and eight introns. The three mRNA splice variants resulting in one transmembrane (muIfnar-2c) and two soluble (muIfnar-2a/2a') mRNA isoforms are generated by alternative RNA processing of the muIfnar-2 gene. Treatment of a range of murine cell lines with a combination of type I and II IFN showed that the muIfnar-2a and -2c mRNA isoforms were up-regulated independently of each other in L929 fibroblasts and hepa-1c1c7 hepatoma cells, but not in M1 myeloid leukaemia cells. Analysis of the 5' flanking region of muIfnar-2 using promoter-luciferase reporter constructs defined three regulatory regions: a region proximal to exon 1, conferring high basal expression, a distal region conferring inducible expression, and a negative regulatory region between the two. These data represent the first promoter analysis of a type I IFN receptor and, taken together with our previous data demonstrating high expression levels and dual biological functions for muIfnar-2a protein, suggests that the regulation of muIfnar-2 isoform expression may be an important way of modulating type I IFN responses.
Hardy
Matthew P
MP
Center for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria 3168, Australia.
Hertzog
Paul J
PJ
Owczarek
Catherine M
CM
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005091:Exons; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007438:Introns; D008565:Membrane Proteins; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; C507964:IFNAR1 protein, human; C508034:Ifnar2 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta