Organization of the mouse RNA-specific adenosine deaminase Adar1 gene 5'-region and demonstration of STAT1-independent, STAT2-dependent transcriptional activation by interferon.
The p150 form of the RNA-specific adenosine deaminase ADAR1 is interferon-inducible and catalyzes A-to-I editing of viral and cellular RNAs. We have characterized mouse genomic clones containing the promoter regions required for Adar1 gene transcription and analyzed interferon induction of the p150 protein using mutant mouse cell lines. Transient transfection analyses using reporter constructs led to the identification of three promoters, one interferon-inducible (P(A)) and two constitutively active (P(B) and P(C)). The TATA-less P(A) promoter, characterized by the presence of a consensus ISRE element and a PKR kinase KCS-like element, directed interferon-inducible reporter expression in rodent and human cells. Interferon induction of p150 was impaired in mouse cells deficient in IFNAR receptor, JAK1 kinase or STAT2 but not STAT1. Whereas Adar1 gene organization involving multiple promoters and alternative exon 1 structures was highly preserved, sequences of the promoters and exon 1 structures were not well conserved between human and mouse.
George
Cyril X
CX
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
Das
Sonali
S
Samuel
Charles E
CE
D000243:Adenosine Deaminase / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D019677:Artificial Gene Fusion; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D017930:Genes, Reporter; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D053613:Janus Kinase 1 / Q000172:deficiency; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D050794:STAT1 Transcription Factor / Q000172:deficiency / Q000378:metabolism*; D050795:STAT2 Transcription Factor / Q000172:deficiency / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
C508032:Ifnar1 protein, mouse; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; C494080:Stat1 protein, mouse; C494085:Stat2 protein, mouse; D053633:Receptor, Interferon alpha-beta; D007372:Interferons; D008156:Luciferases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase
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