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Regulation of alternative splicing by RNA editing

Nature volume 399, pages 75–80 (1999)Cite this article

Abstract

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 inosine1,2,3. 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 (Al) 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.

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Figure 1: Generation of multiple rADAR2 mRNA and protein isoforms by alternative splicing.
Figure 2: Immunoblotting analysis of epitope (Flag)-tagged wild-type and mutant rADAR2 proteins.
Figure 3: Analysis of tissue-specific ADAR2 alternative splicing patterns.
Figure 4: RNA editing and splicing of rat ADAR2 transcripts.
Figure 5: Identification of rADAR2 cis -active regulatory elements.

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Acknowledgements

We thank J. Barnett, J. Patton, B. Wadzinski, C. Desai and members of R.B.E.'s laboratory for critically reading this manuscript. This work was supported by a grant from the NIH.

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  1. Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, 37232-6600, Tennessee, USA

    Susan M. Rueter, T. Renee Dawson & Ronald B. Emeson

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  1. Susan M. Rueter
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  2. T. Renee Dawson
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  3. Ronald B. Emeson
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Correspondence to Ronald B. Emeson.

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Rueter, S., Dawson, T. & Emeson, R. Regulation of alternative splicing by RNA editing. Nature 399, 75–80 (1999). https://doi.org/10.1038/19992

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