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

@article{Bhalla2004ControlOH,
  title={Control of human potassium channel inactivation by editing of a small mRNA hairpin},
  author={Tarun Bhalla and Joshua J C Rosenthal and Miguel Holmgren and R A Reenan},
  journal={Nature Structural \&Molecular Biology},
  year={2004},
  volume={11},
  pages={950-956}
}
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 KV1.1 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… 
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TLDR
The results show that even a minor change in amino acid side-chain chemistry and size can have a dramatic impact on channel biophysics, and that RNA editing is important for fine-tuning the channel’s function.
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It is shown that the channel's in activation gate enters deep into the ion permeation pathway and the very tip establishes a direct hydrophobic interaction with the edited position, allowing the inactivation gate to unbind with much faster kinetics.
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Characterizing the biophysical properties of currents in nine isoforms revealed an unprecedented feature, functional epistasis; biophysical phenotypes of isoforms cannot be explained simply by the consequences of individual editing effects at the four sites.
Characterization of Five RNA Editing Sites in Shab Potassium Channels
TLDR
Results show that both the position of the RNA editing site and the identity of the substituted amino acid are important for channel function.
Mutations underlying Episodic Ataxia type-1 antagonize Kv1.1 RNA editing
TLDR
These studies provide the first evidence that mutations associated with human genetic disorders can affect cis-regulatory elements to alter RNA editing and influence channel properties viaenosine-to-inosine RNA editing.
RNA editing in regulating gene expression in the brain.
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TLDR
A review of how RNA editing affects protein function and higher order physiology in mammals and some of the emerging targets for editing and how this process may be used to regulate nervous function in response to a variable environment are discussed.
Regulation of site-selective A-to-I RNA editing : During mammalian brain development
TLDR
The results suggest that editing controls trafficking of α3-containing receptors and may therefore facilitate the switch of subunit compositions during development as well as the subcellular distribution of α subunits in the adult brain.
Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9
TLDR
It is shown that editing of CaV1.3 mRNA is dependent on a 40 bp RNA duplex formed between exon 41 and an evolutionarily conserved editing site complementary sequence (ECS) located within the preceding intron.
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References

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TLDR
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TLDR
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TLDR
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TLDR
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