Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons
Rapid input-restricted change in gene expression is an important aspect of synaptic plasticity requiring complex mechanisms of post-transcriptional mRNA trafficking and regulation. Small non-coding miRNA are uniquely poised to support these functions by providing a nucleic-acid-based specificity com...
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Veröffentlicht in: | Nucleic acids research 2014-08, Vol.42 (14), p.9195-9208 |
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creator | Goldie, Belinda J Dun, Matthew D Lin, Minjie Smith, Nathan D Verrills, Nicole M Dayas, Christopher V Cairns, Murray J |
description | Rapid input-restricted change in gene expression is an important aspect of synaptic plasticity requiring complex mechanisms of post-transcriptional mRNA trafficking and regulation. Small non-coding miRNA are uniquely poised to support these functions by providing a nucleic-acid-based specificity component for universal-sequence-dependent RNA binding complexes. We investigated the subcellular distribution of these molecules in resting and potassium chloride depolarized human neuroblasts, and found both selective enrichment and depletion in neurites. Depolarization was associated with a neurite-restricted decrease in miRNA expression; a subset of these molecules was recovered from the depolarization medium in nuclease resistant extracellular exosomes. These vesicles were enriched with primate specific miRNA and the synaptic-plasticity-associated protein MAP1b. These findings further support a role for miRNA as neural plasticity regulators, as they are compartmentalized in neurons and undergo activity-associated redistribution or release into the extracellular matrix. |
doi_str_mv | 10.1093/nar/gku594 |
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Small non-coding miRNA are uniquely poised to support these functions by providing a nucleic-acid-based specificity component for universal-sequence-dependent RNA binding complexes. We investigated the subcellular distribution of these molecules in resting and potassium chloride depolarized human neuroblasts, and found both selective enrichment and depletion in neurites. Depolarization was associated with a neurite-restricted decrease in miRNA expression; a subset of these molecules was recovered from the depolarization medium in nuclease resistant extracellular exosomes. These vesicles were enriched with primate specific miRNA and the synaptic-plasticity-associated protein MAP1b. These findings further support a role for miRNA as neural plasticity regulators, as they are compartmentalized in neurons and undergo activity-associated redistribution or release into the extracellular matrix.</description><subject>Cell Line, Tumor</subject><subject>Down-Regulation</subject><subject>Exosomes - chemistry</subject><subject>Exosomes - metabolism</subject><subject>Humans</subject><subject>MicroRNAs - analysis</subject><subject>MicroRNAs - metabolism</subject><subject>Microtubule-Associated Proteins - analysis</subject><subject>Molecular Biology</subject><subject>Nerve Tissue Proteins - analysis</subject><subject>Neurites - chemistry</subject><subject>Neurites - metabolism</subject><subject>Neurons - metabolism</subject><subject>Neurons - physiology</subject><subject>Protein Biosynthesis</subject><subject>Proteome - chemistry</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction</subject><subject>Transcription, Genetic</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkNtKw0AQhhdRbK3e-ACSayF2D7NJcyOU4gmqguj1stlDuzbJht20WJ_eSLXo1cA3__wDH0LnBF8RXLBxI8N4sVrzAg7QkLCMplBk9BANMcM8JRgmA3QS4zvGBAiHYzSgHHM2ARgiNVWd27hum8oYvXKyMzqp3cvTNJHBJK1UK7nokWuSR9mSMjVNcGrZE_Pho69NTIKpjIw9scHXiTatr2Rwnz1ozDr4Jp6iIyuraM5-5gi93d68zu7T-fPdw2w6TxUAdKnmWjFd0klpAXINmSU8N5rkhYWMZqTASudEAS95RktOSw3USqmJzjFhOmMjdL3rbddlbbQyTRdkJdrgahm2wksn_m8atxQLvxFAGM0p7gsudwUq-BiDsftbgsW3atGrFjvVffji77d99Nct-wIQxn38</recordid><startdate>20140818</startdate><enddate>20140818</enddate><creator>Goldie, Belinda J</creator><creator>Dun, Matthew D</creator><creator>Lin, Minjie</creator><creator>Smith, Nathan D</creator><creator>Verrills, Nicole M</creator><creator>Dayas, Christopher V</creator><creator>Cairns, Murray J</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20140818</creationdate><title>Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons</title><author>Goldie, Belinda J ; 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subjects | Cell Line, Tumor Down-Regulation Exosomes - chemistry Exosomes - metabolism Humans MicroRNAs - analysis MicroRNAs - metabolism Microtubule-Associated Proteins - analysis Molecular Biology Nerve Tissue Proteins - analysis Neurites - chemistry Neurites - metabolism Neurons - metabolism Neurons - physiology Protein Biosynthesis Proteome - chemistry RNA, Messenger - metabolism Signal Transduction Transcription, Genetic |
title | Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons |
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