Nervous system-wide profiling of presynaptic mRNAs reveals regulators of associative memory

Sci Rep. 2019 Dec 30;9(1):20314. doi: 10.1038/s41598-019-56908-8.


Presynaptic protein synthesis is important in the adult central nervous system; however, the nervous system-wide set of mRNAs localized to presynaptic areas has yet to be identified in any organism. Here we differentially labeled somatic and synaptic compartments in adult C. elegans with fluorescent proteins, and isolated synaptic and somatic regions from the same population of animals. We used this technique to determine the nervous system-wide presynaptic transcriptome by deep sequencing. Analysis of the synaptic transcriptome reveals that synaptic transcripts are predicted to have specialized functions in neurons. Differential expression analysis identified 542 genes enriched in synaptic regions relative to somatic regions, with synaptic functions conserved in higher organisms. We find that mRNAs for pumilio RNA-binding proteins are abundant in synaptic regions, which we confirmed through high-sensitivity in situ hybridization. Presynaptic PUMILIOs regulate associative memory. Our approach enables the identification of new mechanisms that regulate synaptic function and behavior.

Publication types

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

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Binding Sites
  • Caenorhabditis elegans
  • Central Nervous System / physiology*
  • Fluorescent Antibody Technique
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • Genomics / methods
  • Mammals
  • Memory*
  • Neurons / metabolism
  • Presynaptic Terminals / metabolism*
  • Protein Binding
  • Protein Biosynthesis
  • RNA, Messenger / genetics*
  • RNA-Binding Proteins / metabolism
  • Synapses / metabolism
  • Transcriptome*


  • 3' Untranslated Regions
  • RNA, Messenger
  • RNA-Binding Proteins