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

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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 (P_o) of neuronal SLO-2 is ~50% lower in scyl-1 knockout mutant than wild type. Moreover, human Slo2.2/Slack P_o 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

1. Niu L
2. Liu P
3. Wang Z
4. Chen B
(2019) Slo2 potassium channel function depends on a SCYL1 protein
NCBI Gene Expression Omnibus, GSE141316.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE141316

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Author details

Long-Gang Niu

Department of Neuroscience, University of Connecticut Health Center, Farmington, United States

Competing interests
The authors declare that no competing interests exist.
Ping Liu

Department of Neuroscience, University of Connecticut Health Center, Farmington, United States

Competing interests
The authors declare that no competing interests exist.
Zhao-Wen Wang

Department of Neuroscience, University of Connecticut Health Center, Farmington, United States

Competing interests
The authors declare that no competing interests exist.
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.

"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.

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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.