Referenced in: Kv1.1

Automatically associated channels: Kv1.1

Title: Degradation of high affinity HuD targets releases Kv1.1 mRNA from miR-129 repression by mTORC1.

Authors: Natasha M Sosanya, Peggy P C Huang, Luisa P Cacheaux, Chun Jung Chen, Kathleen Nguyen, Nora I Perrone-Bizzozero, Kimberly F Raab-Graham

Journal, date & volume: J. Cell Biol., 2013 Jul 8 , 202, 53-69

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23836929

Abstract
Little is known about how a neuron undergoes site-specific changes in intrinsic excitability during neuronal activity. We provide evidence for a novel mechanism for mTORC1 kinase-dependent translational regulation of the voltage-gated potassium channel Kv1.1 messenger RNA (mRNA). We identified a microRNA, miR-129, that repressed Kv1.1 mRNA translation when mTORC1 was active. When mTORC1 was inactive, we found that the RNA-binding protein, HuD, bound to Kv1.1 mRNA and promoted its translation. Unexpectedly, inhibition of mTORC1 activity did not alter levels of miR-129 and HuD to favor binding to Kv1.1 mRNA. However, reduced mTORC1 signaling caused the degradation of high affinity HuD target mRNAs, freeing HuD to bind Kv1.1 mRNA. Hence, mTORC1 activity regulation of mRNA stability and high affinity HuD-target mRNA degradation mediates the bidirectional expression of dendritic Kv1.1 ion channels.