Published on Oct. 1, 2004 in Nat Struct Mol Biol volume 11(10).
PubMed ID: 15361858
Genomic recoding by A-->I RNA editing plays an important role in diversifying theproteins involved in electrical excitability. Here, we describe editing of anintronless potassium channel gene. A small region of human K(V)1.1 mRNA sequencedirects efficient modification of one adenosine by human adenosine deaminase actingon RNA 2 (hADAR2). Mutational analysis shows that this region adopts a hairpinstructure. Electrophysiological characterization reveals that the editing event(I/V) profoundly affects channel inactivation conferred by accessory beta subunits.Drosophila melanogaster Shaker channels, mimicking this editing event throughmutation, exhibit a similar effect. In addition, we demonstrate that mRNAs for theparalogous D. melanogaster Shab potassium channel are edited at the same position byfly ADAR-a clear example of convergent evolution driven by adenosine deamination.These results suggest an ancient and key regulatory role for this residue in K(V)channels.