Slo2 potassium channel function depends on RNA editing-regulated expression of a SCYL1 protein

  1. Long-Gang Niu
  2. Ping Liu
  3. Zhao-Wen Wang
  4. Bojun Chen  Is a corresponding author
  1. University of Connecticut Health Center, United States

Abstract

Slo2 potassium channels play important roles in neuronal function, and their mutations in humans may cause epilepsies and cognitive defects. However, it is largely unknown how Slo2 is regulated by other proteins. Here we show that the function of C. elegans Slo2 (SLO-2) depends on adr-1, a gene important to RNA editing. ADR-1 promotes SLO-2 function not by editing the transcripts of slo-2 but those of scyl-1, which encodes an orthologue of mammalian SCYL1. Transcripts of scyl-1 are greatly decreased in adr-1 mutants due to deficient RNA editing at a single adenosine in their 3'-UTR. SCYL-1 physically interacts with SLO-2 in neurons. Single-channel open probability (Po) of neuronal SLO-2 is ~50% lower in scyl-1 knockout mutant than wild type. Moreover, human Slo2.2/Slack Po is doubled by SCYL1 in a heterologous expression system. These results suggest that SCYL-1/SCYL1 is an evolutionarily conserved regulator of Slo2 channels.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 4, 5, 7, 8, 10,and 11.Sequencing data have been deposited in GEO under accession codes GSE141316

The following data sets were generated

Article and author information

Author details

  1. Long-Gang Niu

    Department of Neuroscience, University of Connecticut Health Center, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ping Liu

    Department of Neuroscience, University of Connecticut Health Center, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Zhao-Wen Wang

    Department of Neuroscience, University of Connecticut Health Center, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Bojun Chen

    Department of Neuroscience, University of Connecticut Health Center, Farmington, United States
    For correspondence
    bochen@uchc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1141-9101

Funding

National Institute of General Medical Sciences (R01GM113004)

  • Bojun Chen

National Institute of Mental Health (2R01MH085927)

  • Zhao-Wen Wang

National Institute of Neurological Disorders and Stroke (1R01NS109388)

  • Zhao-Wen Wang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Version history

  1. Received: November 26, 2019
  2. Accepted: April 20, 2020
  3. Accepted Manuscript published: April 21, 2020 (version 1)
  4. Version of Record published: May 1, 2020 (version 2)

Copyright

© 2020, Niu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Long-Gang Niu
  2. Ping Liu
  3. Zhao-Wen Wang
  4. Bojun Chen
(2020)
Slo2 potassium channel function depends on RNA editing-regulated expression of a SCYL1 protein
eLife 9:e53986.
https://doi.org/10.7554/eLife.53986

Share this article

https://doi.org/10.7554/eLife.53986

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