PMID- 10200312
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 8
DP  - 1999 Apr 13
TI  - 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.
PG  - 4621-6
AB  - 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 approximately 150-kDa protein and a constitutively
      expressed N-terminally truncated approximately 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 PC
      and PI. Exon 1B transcripts were initiated from the PC 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 PI
      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 approximately 110-kDa ADAR1 protein (exon 1B) or the interferon-induced
      approximately 150-kDa ADAR1 protein (exon 1A).
FAU - George, C X
AU  - George CX
AD  - Department of Molecular, Cellular, and Developmental Biology, University of
      California, Santa Barbara, CA 93106, USA.
FAU - Samuel, C E
AU  - Samuel CE
LA  - eng
SI  - GENBANK/AF084516
SI  - GENBANK/AF084517
SI  - GENBANK/AF084518
GR  - R01 AI012520/AI/NIAID NIH HHS/United States
GR  - R37 AI012520/AI/NIAID NIH HHS/United States
GR  - AI-12520/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 9008-11-1 (Interferons)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
RN  - EC 3.5.4.4 (ADARB1 protein, human)
RN  - EC 3.5.4.4 (Adenosine Deaminase)
SB  - IM
MH  - Adenosine Deaminase/biosynthesis/*genetics
MH  - *Alternative Splicing
MH  - Amnion/cytology/metabolism
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Chloramphenicol O-Acetyltransferase/biosynthesis
MH  - Enzyme Induction
MH  - Exons
MH  - Female
MH  - Genomic Library
MH  - Humans
MH  - Interferons/*pharmacology
MH  - Introns
MH  - Molecular Sequence Data
MH  - Placenta/enzymology
MH  - Pregnancy
MH  - RNA Editing
MH  - RNA-Binding Proteins
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Alignment
MH  - Sequence Homology, Nucleic Acid
MH  - *Transcription, Genetic
MH  - Transfection
PMC - PMC16382
EDAT- 1999/04/14 00:00
MHDA- 1999/04/14 00:01
CRDT- 1999/04/14 00:00
PHST- 1999/04/14 00:00 [pubmed]
PHST- 1999/04/14 00:01 [medline]
PHST- 1999/04/14 00:00 [entrez]
AID - 10.1073/pnas.96.8.4621 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4621-6. doi: 10.1073/pnas.96.8.4621.