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

Proceedings of the National Academy of Sciences of the United States of America - Tập 96 Số 8 - Trang 4621-4626 - 1999
Cyril X. George1, Charles E. Samuel2,1
1Department of Molecular, Cellular, and Developmental Biology, and Interdepartmental Program of Biochemistry and Molecular Biology, University of California, Santa Barbara, CA 93106
2Department of Molecular, Cellular and Developmental Biology and

Tóm tắt

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 IFN-inducible ≈150-kDa protein and a constitutively expressed N-terminally truncated ≈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 IFN inducible. Cloning and sequence analyses of 5′-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 IFN-treated human amnion cells demonstrated that exon 1B–exon 2 transcripts were synthesized in the absence of IFN 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 ≈110-kDa ADAR1 protein (exon 1B) or the interferon-induced ≈150-kDa ADAR1 protein (exon 1A).

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Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 96 Số 8

4621-4626

Thông tin tác giả