Control of human potassium channel inactivation by editing of a small mRNA hairpin.
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.
Bhalla
Tarun
T
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Rosenthal
Joshua J C
JJ
Holmgren
Miguel
M
Reenan
Robert
R
D000595:Amino Acid Sequence; D000818:Animals; D004331:Drosophila melanogaster; D006801:Humans; D051662:Kv1.1 Potassium Channel; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
C496946:KCNA1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051662:Kv1.1 Potassium Channel