Regulation of the miR-212/132 locus by MSK and CREB in response to neurotrophins.
Résumé
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 if neurotrophins regulate the production of microRNAs, small RNA species that modulate protein translation or mRNA stability, we used deep sequencing to identify brain derived neurotrophic factor (BDNF) induced microRNAs in cultured primary cortical mouse neurons. This revealed that the miR-212/132 cluster contained the microRNAs most responsive to BDNF treatment. This cluster was found to produce four microRNAs; miR-132, miR-132*, miR-212, miR-212*. Using specific inhibitors, mouse models and promoter analysis we have shown that the regulation of the transcription of the miR-212/132 microRNA cluster and the microRNAs derived from it are regulated by the ERK1/2 pathway, via both MSK dependent and independent mechanisms.
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