Activity-dependent spatially localized miRNA maturation in neuronal dendrites

Science. 2017 Feb 10;355(6325):634-637. doi: 10.1126/science.aaf8995.

Abstract

MicroRNAs (miRNAs) regulate gene expression by binding to target messenger RNAs (mRNAs) and preventing their translation. In general, the number of potential mRNA targets in a cell is much greater than the miRNA copy number, complicating high-fidelity miRNA-target interactions. We developed an inducible fluorescent probe to explore whether the maturation of a miRNA could be regulated in space and time in neurons. A precursor miRNA (pre-miRNA) probe exhibited an activity-dependent increase in fluorescence, suggesting the stimulation of miRNA maturation. Single-synapse stimulation resulted in a local maturation of miRNA that was associated with a spatially restricted reduction in the protein synthesis of a target mRNA. Thus, the spatially and temporally regulated maturation of pre-miRNAs can be used to increase the precision and robustness of miRNA-mediated translational repression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendrites / metabolism*
  • Fluorescent Dyes / chemistry
  • Gene Expression Regulation*
  • Hippocampus / cytology
  • Male
  • MicroRNAs / metabolism*
  • Neurons / metabolism*
  • Protein Biosynthesis / genetics*
  • RNA Cleavage
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism
  • Synapses / metabolism

Substances

  • Fluorescent Dyes
  • MIRN181 microRNA, rat
  • MicroRNAs
  • RNA, Messenger
  • Ribonuclease III