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, J. Simon C. Arthur

Research output: Contribution to journalArticle

154 Scopus citations

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 BDNF 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-signal-regulated kinase 1/2) pathway, via bothMSK (mitogen and stress-activated kinase)-dependent and -independent mechanisms.

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

Keywords

  • Brain-derived neurotrophic factor (BDNF)
  • MicroRNA (miRNA)
  • Mitogen- and stress-activated kinase 1 (MSK1)
  • Mitogen- and stress-activated kinase 2 (MSK2)
  • Mitogen-activated protein kinase (MAPK)
  • Neuron

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • 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