期刊
BIOCHEMICAL JOURNAL
卷 428, 期 -, 页码 281-291出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20100024
关键词
brain-derived neurotrophic factor (BDNF); microRNA (miRNA); mitogen-activated protein kinase (MAPK); mitogen- and stress-activated kinase I (MSK1); mitogen- and stress-activated kinase 2 (MSK2); neuron
资金
- Medical Research Council (U.K.)
- Wellcome Trust
- European Union
- Scottish Bioinformatics Research Network
- Astrgeneca
- Boehringer Ingelheim
- GlaxoSmithKline
- Merck-Serono
- Pfizer
- Wellcome Trust Career Development
- MRC [MC_U127081014] Funding Source: UKRI
- Medical Research Council [MC_U127081014] Funding Source: researchfish
Neurotrophins are growth factors that are important in neuronal development and survival as well as synapse formation and plasticity. Many of the effects of neurotrophins are mediated by changes in protein expression as a result of altered transcription or translation. To determine whether neurotrophins regulate the production of microRNAs (miRNAs), small RNA species that modulate protein translation or mRNA stability, we used deep sequencing to identify BDNF (brain-derived neurotrophic factor)-induced miRNAs in cultured primary cortical mouse neurons. This revealed that the miR-212/132 cluster contained the miRNAs most responsive to BDNE treatment. This cluster was found to produce four miRNAs: miR-132, miR-132*, miR-212 and miR-212*. Using specific inhibitors, mouse models and promoter analysis we have shown that the regulation of the transcription of the miR-212/132 miRNA cluster and the miRNAs derived from it are regulated by the ERK1/2 (extracellular-signalregulated kinase 1/2) pathway, via both MSK (mitogen and stressactivated kinase)-dependent and -independent mechanisms.
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