Protein kinase WNK3 regulates the neuronal splicing factor Fox-1.

Lee, A-Young; Chen, Wei; Stippec, Steve; Self, Jon; Yang, Fan; Ding, Xiaojun; Chen, She; Juang, Yu-Chi et al. · Proc Natl Acad Sci U S A · 2012

basic_science · Level V

Where this comes from

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.

Medical subject headings