NMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivo
microRNAs (miRNAs) are major regulators of protein synthesis in the brain. A major goal is to identify changes in miRNA expression underlying protein synthesis-dependent forms of synaptic plasticity such as long-term potentiation (LTP). Previous analyses focused on changes in miRNA levels in total l...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-01-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00285/full |
| _version_ | 1818023612645376000 |
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| author | Balagopal ePai Taweeporn eSiripornmongcolchai Birgitte eBerentsen Ashraf ePakzad Christel eVieuille Ståle ePallesen Maciej ePajak Maciej ePajak T. Ian eSimpson T. Ian eSimpson J Douglas eArmstrong Karin eWibrand Clive R Bramham |
| author_facet | Balagopal ePai Taweeporn eSiripornmongcolchai Birgitte eBerentsen Ashraf ePakzad Christel eVieuille Ståle ePallesen Maciej ePajak Maciej ePajak T. Ian eSimpson T. Ian eSimpson J Douglas eArmstrong Karin eWibrand Clive R Bramham |
| author_sort | Balagopal ePai |
| collection | DOAJ |
| description | microRNAs (miRNAs) are major regulators of protein synthesis in the brain. A major goal is to identify changes in miRNA expression underlying protein synthesis-dependent forms of synaptic plasticity such as long-term potentiation (LTP). Previous analyses focused on changes in miRNA levels in total lysate samples. Here, we asked whether changes in total miRNA accurately reflect changes in the amount of miRNA bound to Argonaute protein within the miRNA-induced silencing complex (miRISC). Ago2 immunoprecipitation was used to isolate RISC-associated miRNAs following high-frequency stimulation (HFS)-induced LTP in the dentate gyrus of anesthetized rats. Using locked-nucleic acid-based PCR cards for high-throughput screening and independent validation by quantitative TaqMan RT-PCR, we identified differential regulation of Ago2-associated and total miRNA expression. The ratio of Ago2/total miRNA expression was regulated bi-directionally in a miRNA-specific manner and was largely dependent on NMDA receptor activation during LTP induction. The present results identify miRNA association with Ago2 as a potential control point in activity-dependent synaptic plasticity in the adult brain. Finally, novel computational analysis for targets of the Ago2-associated miRNAs identifies 21 pathways that are enriched and differentially targeted by the miRNAs including axon guidance, mTOR, MAPK, Ras and LTP. |
| first_indexed | 2024-12-10T03:47:05Z |
| format | Article |
| id | doaj.art-b4a85c28ae8c456dbf75081244e4dabe |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-10T03:47:05Z |
| publishDate | 2014-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-b4a85c28ae8c456dbf75081244e4dabe2022-12-22T02:03:24ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022014-01-01710.3389/fncel.2013.0028571254NMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivoBalagopal ePai0Taweeporn eSiripornmongcolchai1Birgitte eBerentsen2Ashraf ePakzad3Christel eVieuille4Ståle ePallesen5Maciej ePajak6Maciej ePajak7T. Ian eSimpson8T. Ian eSimpson9J Douglas eArmstrong10Karin eWibrand11Clive R Bramham12University of BergenUniversity of BergenUniversity of BergenUniversity of BergenUniversity of BergenUniversity of BergenUniversity of EdinburghJCMBUniversity of EdinburghJCMBUniversity of EdinburghUniversity of BergenUniversity of BergenmicroRNAs (miRNAs) are major regulators of protein synthesis in the brain. A major goal is to identify changes in miRNA expression underlying protein synthesis-dependent forms of synaptic plasticity such as long-term potentiation (LTP). Previous analyses focused on changes in miRNA levels in total lysate samples. Here, we asked whether changes in total miRNA accurately reflect changes in the amount of miRNA bound to Argonaute protein within the miRNA-induced silencing complex (miRISC). Ago2 immunoprecipitation was used to isolate RISC-associated miRNAs following high-frequency stimulation (HFS)-induced LTP in the dentate gyrus of anesthetized rats. Using locked-nucleic acid-based PCR cards for high-throughput screening and independent validation by quantitative TaqMan RT-PCR, we identified differential regulation of Ago2-associated and total miRNA expression. The ratio of Ago2/total miRNA expression was regulated bi-directionally in a miRNA-specific manner and was largely dependent on NMDA receptor activation during LTP induction. The present results identify miRNA association with Ago2 as a potential control point in activity-dependent synaptic plasticity in the adult brain. Finally, novel computational analysis for targets of the Ago2-associated miRNAs identifies 21 pathways that are enriched and differentially targeted by the miRNAs including axon guidance, mTOR, MAPK, Ras and LTP.http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00285/fullDentate GyrusGene ExpressionHippocampusRNA-Induced Silencing ComplexmicroRNAprotein synthesis |
| spellingShingle | Balagopal ePai Taweeporn eSiripornmongcolchai Birgitte eBerentsen Ashraf ePakzad Christel eVieuille Ståle ePallesen Maciej ePajak Maciej ePajak T. Ian eSimpson T. Ian eSimpson J Douglas eArmstrong Karin eWibrand Clive R Bramham NMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivo Frontiers in Cellular Neuroscience Dentate Gyrus Gene Expression Hippocampus RNA-Induced Silencing Complex microRNA protein synthesis |
| title | NMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivo |
| title_full | NMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivo |
| title_fullStr | NMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivo |
| title_full_unstemmed | NMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivo |
| title_short | NMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivo |
| title_sort | nmda receptor dependent regulation of mirna expression and association with argonaute during ltp in vivo |
| topic | Dentate Gyrus Gene Expression Hippocampus RNA-Induced Silencing Complex microRNA protein synthesis |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00285/full |
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