Human RNA-specific adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon inducible

RNA-specific adenosine deaminase (ADAR1) catalyzes the deamination of adenosine to inosine in viral and cellular RNAs. Two size forms of the ADAR1 editing enzyme are known, an IPN-inducible approximate to 150-kDa protein and a constitutively expressed N-terminally truncated approximate to 110-kDa protein. We have now identified alternative exon 1 structures of human ADAR1 transcripts that initiate from unique promoters, one constitutively expressed and the other IBN inducible. Cloning and sequence analyses of S'-rapid amplification of cDNA ends (RACE) cDNAs from human placenta established a linkage between exon 2 of ADAR1 and two alternative exon 1 structures, designated herein as exon 1A and exon 1B. Analysis of RNA isolated from untreated and IPN-treated human amnion cells demonstrated that exon 1B-exon 2 transcripts were synthesized in the absence of IBN and were not significantly altered in amount by IFN treatment. By contrast, exon 1A-exon 2 transcripts were IFN inducible. Transient transfection analysis with reporter constructs led to the identification of two functional promoters, designated P-C and P-I. Exon 1B transcripts were initiated from the P-C promoter whose activity in transient transfection reporter assays was not increased by IFN treatment. The 107-nt exon 1B mapped 14.5 kb upstream of exon 2, The 201-nt exon 1A that mapped 5.4 kb upstream of exon 2 was initiated from the interferon-inducible P-I promoter. These results suggest that two promoters, one IFN inducible and the other not, initiate transcription of the ADAR1 gene, and that alternative splicing of unique exon 1 structures to a common exon 2 junction generates RNA transcripts with the deduced coding capacity for either the constitutively expressed approximate to 110-kDa ADAR1 protein (exon 1B) or the interferon-induced approximate to 150-kDa ADAR1 protein (exon 1A).