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NMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivo.

TitleNMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivo.
Publication TypeJournal Article
Year of Publication2014
AuthorsPai, B, Siripornmongcolchai, T, Berentsen, B, Pakzad, A, Vieuille, C, Pallesen, S, Pajak, M, Simpson, TIan, Armstrong, JDouglas, Wibrand, K, Bramham, CR
JournalFront Cell Neurosci
Volume7
Pagination285
Date Published2014 Jan 13
ISSN1662-5102
Abstract

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 bidirectionally in a miRNA-specific manner and was largely dependent on N-methyl-D-aspartate receptor (NMDA) 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.

DOI10.3389/fncel.2013.00285
Alternate JournalFront Cell Neurosci
PubMed ID24454279
PubMed Central IDPMC3888942
Grant ListBB/I004491/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom