Protein kinase WNK3 regulates the neuronal splicing factor Fox-1

A. Young Lee, Wei Chen, Steve Stippec, Jon Self, Fan Yang, Xiaojun Ding, She Chen, Yu Chi Juang, Melanie H. Cobb

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

We report an action of the protein kinase WNK3 on the neuronal mRNA splicing factor Fox-1. Fox-1 splices mRNAs encoding proteins important in synaptic transmission and membrane excitation. WNK3, implicated in the control of neuronal excitability through actions on ion transport, binds Fox-1 and inhibits its splicing activity in a kinase activity-dependent manner. Phosphorylation of Fox-1 by WNK3 does not change its RNA binding capacity; instead, WNK3 increases the cytoplasmic localization of Fox-1, thereby suppressing Fox-1-dependent splicing. These findings demonstrate a role of WNK3 in RNA processing. Considering the implication of WNK3 and Fox-1 in disorders of neuronal development such as autism, WNK3 may offer a target for treatment of Fox-1-induced disease.

Original languageEnglish (US)
Pages (from-to)16841-16846
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number42
DOIs
Publication statusPublished - Oct 16 2012

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Keywords

  • Cytoplasmic retention
  • FMNL3

ASJC Scopus subject areas

  • General

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