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

doi:10.1042/BJ20100024

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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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 language	English
Pages (from-to)	281-291
Number of pages	11
Journal	Biochemical Journal
Volume	428
Issue number	2
DOIs	https://doi.org/10.1042/BJ20100024
Publication status	Published - 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

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10.1042/BJ20100024

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

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.",

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",

author = "Judit Remenyi and Hunter, {Christopher J.} and Christian Cole and Hideaki Ando and Soren Impey and Monk, {Claire E.} and Martin, {Kirsty J.} and Barton, {Geoffrey J.} and Gyorgy Hutvagner and Arthur, {J. Simon C.}",

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AU - Hunter, Christopher J.

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AU - Ando, Hideaki

AU - Impey, Soren

AU - Monk, Claire E.

AU - Martin, Kirsty J.

AU - Barton, Geoffrey J.

AU - Hutvagner, Gyorgy

AU - Arthur, J. Simon C.

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AB - 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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KW - INHIBITOR

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JO - Biochemical Journal

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

Abstract

Keywords

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