Extensive editing of mRNAs for the squid delayed rectifier K+ channel regulates subunit tetramerization.
We report the extensive editing of mRNAs that encode the classical delayed rectifier K+ channel (SqK(v)1.1A) in the squid giant axon. Using a quantitative RNA editing assay, 14 adenosine to guanine transitions were identified, and editing efficiency varied tremendously between positions. Interestingly, half of the sites are targeted to the T1 domain, important for subunit assembly. Other sites occur in the channel's transmembrane spans. The effects of editing on K+ channel function are elaborate. Edited codons affect channel gating, and several T1 sites regulate functional expression as well. In particular, the edit R87G, a phylogenetically conserved position, reduces expression close to 50-fold by regulating the channel's ability to form tetramers. These data suggest that RNA editing plays a dynamic role in regulating action potential repolarization in the giant axon.
Rosenthal
Joshua J C
JJ
Department of Physiology, UCLA School of Medicine, USA.
Bezanilla
Francisco
F
D000200:Action Potentials / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D001483:Base Sequence / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D049832:Decapodiformes / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016678:Genome; D051662:Kv1.1 Potassium Channel; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000378:metabolism*; D009431:Neural Conduction / Q000235:genetics; D009865:Oocytes; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D017393:RNA Editing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis
D046911:Macromolecular Substances; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051662:Kv1.1 Potassium Channel