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

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 both MSK (mitogen and stress-activated kinase)-dependent and -independent mechanisms.

[1]  P. Sharp,et al.  Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125 b and miR-132 , 2010 .

[2]  H. Tsukamoto,et al.  MeCP2 controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis. , 2010, Gastroenterology.

[3]  Hideaki Ando,et al.  An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling , 2010, Molecular and Cellular Neuroscience.

[4]  G. Barton,et al.  Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. , 2009, RNA.

[5]  K. Waters,et al.  MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirT1. , 2009, Molecular endocrinology.

[6]  J. Arthur,et al.  Generation of a conditional CREB Ser133Ala knockin mouse , 2009, Genesis.

[7]  Z. Mourelatos,et al.  Emerging roles of microRNAs as molecular switches in the integrated circuit of the cancer cell. , 2009, RNA.

[8]  Hiroshi I. Suzuki,et al.  Modulation of microRNA processing by p53 , 2009, Nature.

[9]  W. Filipowicz,et al.  Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. , 2009, Current opinion in cell biology.

[10]  R. Speich,et al.  Interleukin-6 Modulates the Expression of the Bone Morphogenic Protein Receptor Type II Through a Novel STAT3–microRNA Cluster 17/92 Pathway , 2009, Circulation research.

[11]  M. Rosenfeld,et al.  The RNA-binding Protein KSRP Promotes the Biogenesis of a Subset of miRNAs , 2016 .

[12]  C. Semple,et al.  Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops , 2008, Molecular cell.

[13]  J. Arthur,et al.  The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling , 2008, Nature Immunology.

[14]  I. Bozzoni,et al.  Primary microRNA transcripts are processed co-transcriptionally , 2008, Nature Structural &Molecular Biology.

[15]  Oliver Hobert,et al.  Molecular architecture of a miRNA-regulated 3' UTR. , 2008, RNA.

[16]  Hideaki Ando,et al.  An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP , 2008, Proceedings of the National Academy of Sciences.

[17]  A. Hamilton,et al.  Improved northern blot method for enhanced detection of small RNA , 2008, Nature Protocols.

[18]  François Chevenet,et al.  OligoHeatMap (OHM): an online tool to estimate and display hybridizations of oligonucleotides onto DNA sequences , 2008, Nucleic Acids Res..

[19]  G. Daley,et al.  Selective Blockade of MicroRNA Processing by Lin28 , 2008, Science.

[20]  Stijn van Dongen,et al.  miRBase: tools for microRNA genomics , 2007, Nucleic Acids Res..

[21]  A. Hata,et al.  SMAD proteins control DROSHA-mediated microRNA maturation , 2008, Nature.

[22]  Oliver Hobert,et al.  UTR ′ Molecular architecture of a miRNA-regulated 3 Material Supplemental , 2008 .

[23]  P. Cohen,et al.  The selectivity of protein kinase inhibitors: a further update. , 2007, The Biochemical journal.

[24]  Gail Mandel,et al.  Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA , 2007, Nature Neuroscience.

[25]  S. Guil,et al.  The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a , 2007, Nature Structural &Molecular Biology.

[26]  P. Cohen,et al.  BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. , 2007, The Biochemical journal.

[27]  L. Reichardt,et al.  Neurotrophin-regulated signalling pathways , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[28]  Oliver Hobert,et al.  Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions , 2006, Nature Structural &Molecular Biology.

[29]  D. Baltimore,et al.  NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses , 2006, Proceedings of the National Academy of Sciences.

[30]  F. Lee,et al.  Neurotrophin signalling in health and disease. , 2006, Clinical science.

[31]  Olga Varlamova,et al.  A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Arthur,et al.  MSKs are required for the transcription of the nuclear orphan receptors Nur77, Nurr1 and Nor1 downstream of MAPK signalling. , 2005, The Biochemical journal.

[33]  V. Kim.  MicroRNA biogenesis: coordinated cropping and dicing , 2005, Nature Reviews Molecular Cell Biology.

[34]  R. Russell,et al.  Principles of MicroRNA–Target Recognition , 2005, PLoS biology.

[35]  R. Shiekhattar,et al.  The Microprocessor complex mediates the genesis of microRNAs , 2004, Nature.

[36]  G. Hannon,et al.  Processing of primary microRNAs by the Microprocessor complex , 2004, Nature.

[37]  U. Moens,et al.  What turns CREB on? , 2004, Cellular signalling.

[38]  J. M. Thomson,et al.  Argonaute2 Is the Catalytic Engine of Mammalian RNAi , 2004, Science.

[39]  T. Tuschl,et al.  Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. , 2004, Molecular cell.

[40]  J. Blenis,et al.  ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions , 2004, Microbiology and Molecular Biology Reviews.

[41]  S. Impey,et al.  Mitogen- and Stress-Activated Protein Kinase 1 Mediates cAMP Response Element-Binding Protein Phosphorylation and Activation by Neurotrophins , 2004, The Journal of Neuroscience.

[42]  R. Durbin,et al.  GeneWise and Genomewise. , 2004, Genome research.

[43]  Enno Ohlebusch,et al.  Replacing suffix trees with enhanced suffix arrays , 2004, J. Discrete Algorithms.

[44]  U. Kutay,et al.  Nuclear Export of MicroRNA Precursors , 2004, Science.

[45]  R. Segal,et al.  Selectivity in neurotrophin signaling: theme and variations. , 2003, Annual review of neuroscience.

[46]  V. Kim,et al.  The nuclear RNase III Drosha initiates microRNA processing , 2003, Nature.

[47]  G. Hutvagner,et al.  A microRNA in a Multiple-Turnover RNAi Enzyme Complex , 2002, Science.

[48]  P. Cohen,et al.  MSK1 and MSK2 Are Required for the Mitogen- and Stress-Induced Phosphorylation of CREB and ATF1 in Fibroblasts , 2002, Molecular and Cellular Biology.

[49]  M. Mann,et al.  miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. , 2002, Genes & development.

[50]  C. Damsky,et al.  β1-Class Integrins Regulate the Development of Laminae and Folia in the Cerebral and Cerebellar Cortex , 2001, Neuron.

[51]  Marc Montminy,et al.  Transcriptional regulation by the phosphorylation-dependent factor CREB , 2001, Nature Reviews Molecular Cell Biology.

[52]  A. Pasquinelli,et al.  A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNA , 2001, Science.

[53]  A. Patapoutian,et al.  Trk receptors: mediators of neurotrophin action , 2001, Current Opinion in Neurobiology.

[54]  Philip R. Cohen,et al.  MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells , 2000, FEBS letters.

[55]  L. Greene,et al.  Neurotrophin signaling via Trks and p75. , 1999, Experimental cell research.

[56]  Calyampudi R. Rao,et al.  Linear Statistical Inference and Its Applications. , 1975 .