Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132
MicroRNAs (miRNAs) are noncoding RNAs that suppress translation of specific mRNAs. The miRNA machinery interacts with fragile X mental retardation protein (FMRP), which functions as translational repressor. We show that miR-125b and miR-132, as well as several other miRNAs, are associated with FMRP...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2015
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| Online Access: | http://hdl.handle.net/1721.1/96085 https://orcid.org/0000-0003-1465-1691 |
| _version_ | 1811080078059110400 |
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| author | Edbauer, Dieter Neilson, Joel R. Foster, Kelly A. Wang, Chi-Fong Seeburg, Daniel P. Batterton, Matthew N. Tada, Tomoko Dolan, Bridget M. Sharp, Phillip A. Sheng, Morgan Hwa-Tze |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Edbauer, Dieter Neilson, Joel R. Foster, Kelly A. Wang, Chi-Fong Seeburg, Daniel P. Batterton, Matthew N. Tada, Tomoko Dolan, Bridget M. Sharp, Phillip A. Sheng, Morgan Hwa-Tze |
| author_sort | Edbauer, Dieter |
| collection | MIT |
| description | MicroRNAs (miRNAs) are noncoding RNAs that suppress translation of specific mRNAs. The miRNA machinery interacts with fragile X mental retardation protein (FMRP), which functions as translational repressor. We show that miR-125b and miR-132, as well as several other miRNAs, are associated with FMRP in mouse brain. miR-125b and miR-132 had largely opposing effects on dendritic spine morphology and synaptic physiology in hippocampal neurons. FMRP knockdown ameliorates the effect of miRNA overexpression on spine morphology. We identified NMDA receptor subunit NR2A as a target of miR-125b and show that NR2A mRNA is specifically associated with FMRP in brain. In hippocampal neurons, NR2A expression is negatively regulated through its 3′ UTR by FMRP, miR-125b, and Argonaute 1. Regulation of NR2A 3′UTR by FMRP depends in part on miR-125b. Because NMDA receptor subunit composition profoundly affects synaptic plasticity, these observations have implications for the pathophysiology of fragile X syndrome, in which plasticity is altered. |
| first_indexed | 2024-09-23T11:25:28Z |
| format | Article |
| id | mit-1721.1/96085 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:25:28Z |
| publishDate | 2015 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/960852022-09-27T19:24:52Z Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 Edbauer, Dieter Neilson, Joel R. Foster, Kelly A. Wang, Chi-Fong Seeburg, Daniel P. Batterton, Matthew N. Tada, Tomoko Dolan, Bridget M. Sharp, Phillip A. Sheng, Morgan Hwa-Tze Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Koch Institute for Integrative Cancer Research at MIT Edbauer, Dieter Neilson, Joel R. Foster, Kelly A. Wang, Chi-Fong Seeburg, Daniel P. Batterton, Matthew N. Tada, Tomoko Dolan, Bridget M. Sharp, Phillip A. Sheng, Morgan MicroRNAs (miRNAs) are noncoding RNAs that suppress translation of specific mRNAs. The miRNA machinery interacts with fragile X mental retardation protein (FMRP), which functions as translational repressor. We show that miR-125b and miR-132, as well as several other miRNAs, are associated with FMRP in mouse brain. miR-125b and miR-132 had largely opposing effects on dendritic spine morphology and synaptic physiology in hippocampal neurons. FMRP knockdown ameliorates the effect of miRNA overexpression on spine morphology. We identified NMDA receptor subunit NR2A as a target of miR-125b and show that NR2A mRNA is specifically associated with FMRP in brain. In hippocampal neurons, NR2A expression is negatively regulated through its 3′ UTR by FMRP, miR-125b, and Argonaute 1. Regulation of NR2A 3′UTR by FMRP depends in part on miR-125b. Because NMDA receptor subunit composition profoundly affects synaptic plasticity, these observations have implications for the pathophysiology of fragile X syndrome, in which plasticity is altered. Deutsche Forschungsgemeinschaft (ED157/1, postdoctoral fellowship) National Cancer Institute (U.S.) (NCI PO1-CA42063) National Cancer Institute (U.S.) (NCI P30-CA14051) National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant) National Cancer Institute (U.S.) (NCI K99-CA131474) Howard Hughes Medical Institute (Investigator) 2015-03-19T17:13:54Z 2015-03-19T17:13:54Z 2010-02 Article http://purl.org/eprint/type/JournalArticle 08966273 http://hdl.handle.net/1721.1/96085 Edbauer, Dieter, Joel R. Neilson, Kelly A. Foster, Chi-Fong Wang, Daniel P. Seeburg, Matthew N. Batterton, Tomoko Tada, Bridget M. Dolan, Phillip A. Sharp, and Morgan Sheng. “Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132.” Neuron 65, no. 3 (February 2010): 373–384. © 2010 Elsevier Inc. https://orcid.org/0000-0003-1465-1691 en_US http://dx.doi.org/10.1016/j.neuron.2010.01.005 Neuron Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier B.V. Elsevier |
| spellingShingle | Edbauer, Dieter Neilson, Joel R. Foster, Kelly A. Wang, Chi-Fong Seeburg, Daniel P. Batterton, Matthew N. Tada, Tomoko Dolan, Bridget M. Sharp, Phillip A. Sheng, Morgan Hwa-Tze Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 |
| title | Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 |
| title_full | Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 |
| title_fullStr | Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 |
| title_full_unstemmed | Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 |
| title_short | Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 |
| title_sort | regulation of synaptic structure and function by fmrp associated micrornas mir 125b and mir 132 |
| url | http://hdl.handle.net/1721.1/96085 https://orcid.org/0000-0003-1465-1691 |
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