Human RNA-specific adenosine deaminase (ADAR1) gene specifies transcripts that initiate from a constitutively active alternative promoter

The human ADAR1 gene specifies two size forms of RNA-specific adenosine deaminase, an interferon (IFN) inducible similar to 150 kDa protein and a constitutively expressed N-terminally truncated similar to 110 kDa protein, encoded by transcripts with alternative exon 1 structures that initiate from different promoters. We have now identified a new class of ADAR1 transcripts, with alternative 5'-structures and a deduced coding capacity for the similar to 110 kDa protein. Nuclease protection and 5'-rapid amplification of cDNA ends (5'-RACE) revealed five major ADAR1 transcriptional start sites that mapped within the previously identified and unusually large (similar to1.6 kb) exon 2. These transcripts were observed with RNA from human amnion U cells and placenta tissue. Their abundance was not affected by IFN-a treatment of U cells in culture. Transfection analysis identified a functional promoter within human genomic DNA that mapped to the proximal exon 2 region of the ADAR1 gene. Promoter activity was not affected by IFN. These results suggest that transcripts encoding the constitutively expressed similar to 110 kDa form of the ADAR1 editing enzyme are initiated from multiple promoters, including one within exon 2, that collectively contribute to the high basal level of deaminase activity observed in nuclei of mammalian cells. (C) 2000 Elsevier Science B.V. All rights reserved.