Regulation of alternative splicing by RNA editing.
The enzyme ADAR2 is a double-stranded RNA-specific adenosine deaminase which is involved in the editing of mammalian messenger RNAs by the site-specific conversion of adenosine to inosine. Here we identify several rat ADAR2 mRNAs produced as a result of two distinct alternative splicing events. One such splicing event uses a proximal 3' acceptor site, adding 47 nucleotides to the ADAR2 coding region, changing the predicted reading frame of the mature ADAR2 transcript. Nucleotide-sequence analysis of ADAR2 genomic DNA revealed the presence of adenosine-adenosine (AA) and adenosine-guanosine (AG) dinucleotides at these proximal and distal alternative 3' acceptor sites, respectively. Use of the proximal 3' acceptor depends upon the ability of ADAR2 to edit its own pre-mRNA, converting the intronic AA to an adenosine-inosine (AI) dinucleotide which effectively mimics the highly conserved AG sequence normally found at 3' splice junctions. Our observations indicate that RNA editing can serve as a mechanism for regulating alternative splicing and they suggest a novel strategy by which ADAR2 can modulate its own expression.
Rueter
S M
SM
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6600, USA.
Dawson
T R
TR
Emeson
R B
RB
D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000235:genetics*; D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA; D015971:Gene Expression Regulation, Enzymologic; D006151:Guanosine / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017393:RNA Editing / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D006151:Guanosine; D004247:DNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D000241:Adenosine