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

TitleNervous system-wide profiling of presynaptic mRNAs reveals regulators of associative memory.
Publication TypeJournal Article
Year of Publication2019
AuthorsArey, RN, Kaletsky, R, Murphy, CT
JournalSci Rep
Date Published2019 Dec 30
Keywords3' Untranslated Regions, Animals, Binding Sites, Caenorhabditis elegans, Central Nervous System, Fluorescent Antibody Technique, Gene Expression Profiling, Gene Expression Regulation, Genome-Wide Association Study, Genomics, Mammals, Memory, Neurons, Presynaptic Terminals, Protein Binding, Protein Biosynthesis, RNA, Messenger, RNA-Binding Proteins, Synapses, Transcriptome

<p>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.</p>

Alternate JournalSci Rep
PubMed ID31889133
PubMed Central IDPMC6937282
Grant ListF32 AG046106 / AG / NIA NIH HHS / United States
DP2 OD004402 / OD / NIH HHS / United States
R01 AG034446 / AG / NIA NIH HHS / United States
AWD1005048 / / Howard Hughes Medical Institute (HHMI) / International