Identification of a cis-acting element that localizes mRNA to synapses

Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4639-44. doi: 10.1073/pnas.1116269109. Epub 2012 Mar 1.

Abstract

Messenger RNA (mRNA) localization and regulated translation can spatially restrict gene expression to each of the thousands of synaptic compartments formed by a single neuron. Although cis-acting RNA elements have been shown to direct localization of mRNAs from the soma into neuronal processes, less is known about signals that target transcripts specifically to synapses. In Aplysia sensory-motor neuronal cultures, synapse formation rapidly redistributes the mRNA encoding the peptide neurotransmitter sensorin from neuritic shafts into synapses. We find that the export of sensorin mRNA from soma to neurite and the localization to synapse are controlled by distinct signals. The 3' UTR is sufficient for export into distal neurites, whereas the 5' UTR is required for concentration of reporter mRNA at synapses. We have identified a 66-nt element in the 5' UTR of sensorin that is necessary and sufficient for synaptic mRNA localization. Mutational and chemical probing analyses are consistent with a role for secondary structure in this process.

Publication types

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

MeSH terms

  • 5' Untranslated Regions
  • Animals
  • Aplysia
  • DNA Mutational Analysis
  • Electrophysiology / methods
  • Genes, Reporter
  • In Situ Hybridization, Fluorescence
  • Neurons / metabolism
  • Neuropeptides / metabolism*
  • Neurotransmitter Agents / metabolism
  • Nucleic Acid Conformation
  • Oligonucleotides, Antisense / metabolism
  • RNA, Messenger / metabolism*
  • Sequence Analysis, RNA
  • Synapses / metabolism

Substances

  • 5' Untranslated Regions
  • Neuropeptides
  • Neurotransmitter Agents
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • sensorin A protein, Aplysia