Control of human potassium channel inactivation by editing of a small mRNA hairpin

Nat Struct Mol Biol. 2004 Oct;11(10):950-6. doi: 10.1038/nsmb825. Epub 2004 Sep 7.

Abstract

Genomic recoding by A-->I RNA editing plays an important role in diversifying the proteins involved in electrical excitability. Here, we describe editing of an intronless potassium channel gene. A small region of human K(V)1.1 mRNA sequence directs efficient modification of one adenosine by human adenosine deaminase acting on RNA 2 (hADAR2). Mutational analysis shows that this region adopts a hairpin structure. 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 through mutation, exhibit a similar effect. In addition, we demonstrate that mRNAs for the paralogous D. melanogaster Shab potassium channel are edited at the same position by fly 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.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drosophila melanogaster
  • Humans
  • Kv1.1 Potassium Channel
  • Molecular Sequence Data
  • Potassium Channels / chemistry
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • RNA Editing*
  • RNA, Messenger / genetics*
  • Sequence Homology, Amino Acid

Substances

  • KCNA1 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • RNA, Messenger
  • Kv1.1 Potassium Channel