Regulation of the miR-212/132 locus by MSK1 and CREB in response to neurotrophins

Judit Remenyi, Christopher J. Hunter, Christian Cole, Hideaki Ando, Soren Impey, Claire E. Monk, Kirsty J. Martin, Geoffrey J. Barton, Gyorgy Hutvagner (Lead / Corresponding author), J. Simon C. Arthur (Lead / Corresponding author)

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    152 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)281-291
    Number of pages11
    JournalBiochemical Journal
    Volume428
    Issue number2
    DOIs
    Publication statusPublished - 1 Jun 2010

    Keywords

    • 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
    • INDUCED MICRORNA
    • RNA
    • PHOSPHORYLATION
    • SELECTIVITY
    • BIOGENESIS
    • ARGONAUTE2
    • EXPRESSION
    • MATURATION
    • INHIBITOR
    • RECEPTORS

    Cite this

    Remenyi, J., Hunter, C. J., Cole, C., Ando, H., Impey, S., Monk, C. E., Martin, K. J., Barton, G. J., Hutvagner, G., & Arthur, J. S. C. (2010). Regulation of the miR-212/132 locus by MSK1 and CREB in response to neurotrophins. Biochemical Journal, 428(2), 281-291. https://doi.org/10.1042/BJ20100024