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

Niu, Long-Gang; Liu, Ping; Wang, Zhao-Wen; Chen, Bojun · Elife · 2020

basic_science · Level V

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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 <i>C. elegans</i> Slo2 (SLO-2) depends on <i>adr-1</i>, a gene important to RNA editing. ADR-1 promotes SLO-2 function not by editing the transcripts of <i>slo-2</i> but those of <i>scyl-1</i>, which encodes an orthologue of mammalian SCYL1. Transcripts of <i>scyl-1</i> are greatly decreased in <i>adr-1</i> 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 (<i>P<sub>o</sub></i>) of neuronal SLO-2 is ~50% lower in <i>scyl-1</i> knockout mutant than wild type. Moreover, human Slo2.2/Slack <i>P<sub>o</sub></i> is doubled by SCYL1 in a heterologous expression system. These results suggest that SCYL-1/SCYL1 is an evolutionarily conserved regulator of Slo2 channels.

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