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

J Cell Biol. 2013 Jul 8;202(1):53-69. doi: 10.1083/jcb.201212089.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • ELAV Proteins / genetics
  • ELAV Proteins / metabolism*
  • ELAV-Like Protein 4
  • Enzyme Activation
  • HEK293 Cells
  • Humans
  • Kv1.1 Potassium Channel / genetics
  • Kv1.1 Potassium Channel / metabolism*
  • Mechanistic Target of Rapamycin Complex 1
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Multiprotein Complexes
  • Neuronal Plasticity
  • Neurons / metabolism
  • Protein Biosynthesis
  • Proteins / genetics
  • Proteins / metabolism*
  • Proteolysis*
  • RNA Processing, Post-Transcriptional
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Rats
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases
  • Transfection

Substances

  • ELAV Proteins
  • ELAV-Like Protein 4
  • Elavl4 protein, rat
  • Kcna1 protein, rat
  • MicroRNAs
  • Multiprotein Complexes
  • Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Kv1.1 Potassium Channel
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1