Bergen Open Research Archive

Modulation of the Ago2-Associated microRNA Induced Silencing Complex during Long-Term Potentiation in the Rat Dentate Gyrus in Vivo

Bergen Open Research Archive

Show simple item record Vieuille, Christel Marie 2012-08-09T11:47:24Z 2012-08-09T11:47:24Z 2012-05-30 2012-05-30 en
dc.description.abstract Synaptic plasticity is defined as the ability of a neuronal synapse to change in strength, and is believed to be the basis of learning and memory. An example of synaptic plasticity, by far the most studied, is long-term potentiation (LTP): a stable, activity-induced increase in synaptic efficacy. LTP requires de novo gene expression, protein synthesis and protein degradation. Transcriptional and post-transcriptional regulation controls new protein expression. In the past decade, small non-coding RNAs called microRNAs have emerged as key regulators of translation. MicroRNAs bind to target mRNAs by complementary binding and recruit a protein complex to mediate mRNA silencing. This complex is known as the microRNAinduced silencing complex (miRISC). The goals of this study were to investigate the composition of the miRISC in the rat dentate gyrus in vivo, to study modulation of the miRISC during LTP, and to uncover new candidate binding partners of Ago2. LTP was induced by HFS of the medial perforant path. The miRISC was isolated by immunoprecipitation of its core component, the protein Argonaute 2 (Ago2). Five proteins thought to bind Ago2 were analyzed by co-immunoprecipitation with Ago2. These proteins were GW182, the RNase III enzyme, Dicer, the RNA-binding protein, FMRP, and the RNA helicases, MOV10 and DDX6. DDX6 was the only protein found to be reliably associated with Ago2, even though all the proteins were detected in association with Ago2 in HEK cells expressing EGFP-Ago2. DDX6 was non-significantly dissociated from Ago2 during LTP. In the total lysate, none of the analyzed proteins were significantly modulated during LTP. Nevertheless, Argonaute 2 and GW182 were non-significantly upregulated, and MOV10 was non-significantly downregulated during LTP. The study does not show a significant remodeling of the miRISC during LTP, but neither does it exclude this possibility. Immunoprecipitated samples were analyzed by mass spectrometry. New candidate Ago2 binding partners were uncovered, such as the proteins DDX1 and FXR1, homologs of DDX6 and FMRP. A protein important for translation, poly-A-binding protein 1 (PABP1), was also detected. en
dc.format.extent 1193170 bytes en
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher The University of Bergen en
dc.rights Copyright the author. All rights reserved en
dc.subject microRNA en
dc.subject Hippocampus en
dc.subject Argonaute en
dc.title Modulation of the Ago2-Associated microRNA Induced Silencing Complex during Long-Term Potentiation in the Rat Dentate Gyrus in Vivo en
dc.type Master thesis en Master i Medisinsk biologi en
dc.type.course BMED395 en
dc.subject.nsi VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Neurology: 752 en
dc.subject.archivecode Mastergrad en
dc.subject.nus 751910 en
dc.type.program MAMD-MEDBI en

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