Regulation of alternative splicing by RNA editing

Nature. 1999 May 6;399(6731):75-80. doi: 10.1038/19992.

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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / metabolism
  • Adenosine Deaminase / genetics*
  • Alternative Splicing / physiology*
  • Animals
  • Base Sequence
  • Cell Line
  • DNA
  • Gene Expression Regulation, Enzymologic
  • Guanosine / metabolism
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • RNA Editing / physiology*
  • RNA, Messenger / genetics
  • RNA-Binding Proteins
  • Rats
  • Transfection
  • Tumor Cells, Cultured

Substances

  • RNA, Messenger
  • RNA-Binding Proteins
  • Guanosine
  • DNA
  • ADARB1 protein, human
  • Adenosine Deaminase
  • Adenosine