Mef2-mediated transcription of the miR379-410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels

被引:312
作者
Fiore, Roberto [1 ,2 ]
Khudayberdiev, Sharof [1 ,2 ]
Christensen, Mette [1 ,2 ,3 ]
Siegel, Gabriele [1 ,2 ]
Flavell, Steven W. [4 ]
Kim, Tae-Kyung [4 ]
Greenberg, Michael E. [4 ]
Schratt, Gerhard [1 ,2 ]
机构
[1] Heidelberg Univ, Interdisziplinares Zentrum Neurowissensch, Jr Grp SFB488, D-69210 Heidelberg, Germany
[2] Heidelberg Univ, Inst Neuroanat, D-69210 Heidelberg, Germany
[3] Univ Copenhagen, Wilhelm Johannsen Ctr Funct Genome Res, Dept Cellular & Mol Med, Blegdamsvej, Denmark
[4] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
关键词
dendritogenesis; Mef2; microRNA; neuronal activity; Pumilio; SYNAPTIC PLASTICITY; DENDRITIC GROWTH; MICRORNA; MEF2; MECHANISMS; DATABASE; RNA;
D O I
10.1038/emboj.2009.10
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neuronal activity orchestrates the proper development of the neuronal circuitry by regulating both transcriptional and post-transcriptional gene expression programmes. How these programmes are coordinated, however, is largely unknown. We found that the transcription of miR379-410, a large cluster of brain-specific microRNAs (miRNAs), is induced by increasing neuronal activity in primary rat neurons. Results from chromatin immunoprecipitation and luciferase reporter assays suggest that binding of the transcription factor myocyte enhancing factor 2 (Mef2) upstream of miR379-410 is necessary and sufficient for activity-dependent transcription of the cluster. Mef2-induced expression of at least three individual miRNAs of the miR379-410 cluster is required for activity-dependent dendritic outgrowth of hippocampal neurons. One of these miRNAs, the dendritic miR-134, promotes outgrowth by inhibiting translation of the mRNA encoding for the translational repressor Pumilio2. In summary, we have described a novel regulatory pathway that couples activity-dependent transcription to miRNA-dependent translational control of gene expression during neuronal development.
引用
收藏
页码:697 / 710
页数:14
相关论文
共 48 条
  • [1] From mRNP trafficking to spine dysmorphogenesis: The roots of fragile X syndrome
    Bagni, C
    Greenough, WT
    [J]. NATURE REVIEWS NEUROSCIENCE, 2005, 6 (05) : 376 - 387
  • [2] Dopamine-mediated regulation of corticostriatal synaptic plasticity
    Calabresi, Paolo
    Picconi, Barbara
    Tozzi, Alessandro
    Di Filippo, Massimiliano
    [J]. TRENDS IN NEUROSCIENCES, 2007, 30 (05) : 211 - 219
  • [3] Identification of Synaptic Targets of Drosophila Pumilio
    Chen, Gengxin
    Li, Wanhe
    Zhang, Qing-Shuo
    Regulski, Michael
    Sinha, Nishi
    Barditch, Jody
    Tully, Tim
    Krainer, Adrian R.
    Zhang, Michael Q.
    Dubnau, Josh
    [J]. PLOS COMPUTATIONAL BIOLOGY, 2008, 4 (02)
  • [4] Regulation of dendritic development by neuronal activity
    Chen, YC
    Ghosh, A
    [J]. JOURNAL OF NEUROBIOLOGY, 2005, 64 (01): : 4 - 10
  • [5] microRNA modulation of circadian-clock period and entrainment
    Cheng, Hai-Ying M.
    Papp, Joseph W.
    Varlamova, Olga
    Dziema, Heather
    Russell, Brandon
    Curfman, John P.
    Nakazawa, Takanobu
    Shimizu, Kimiko
    Okamura, Hitoshi
    Impey, Soren
    Obrietan, Karl
    [J]. NEURON, 2007, 54 (05) : 813 - 829
  • [6] MicroRNA function in neuronal development, plasticity and disease
    Fiore, Roberto
    Siegel, Gabriele
    Schratt, Gerhard
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2008, 1779 (08): : 471 - 478
  • [7] Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system
    Flavell, Steven W.
    Greenberg, Michael E.
    [J]. ANNUAL REVIEW OF NEUROSCIENCE, 2008, 31 : 563 - 590
  • [8] Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number
    Flavell, SW
    Cowan, CW
    Kim, TK
    Greer, PL
    Lin, YX
    Paradis, S
    Griffith, EC
    Hu, LS
    Chen, CF
    Greenberg, ME
    [J]. SCIENCE, 2006, 311 (5763) : 1008 - 1012
  • [9] Origin, evolution, and biological role of miRNA cluster in DLK-DIO3 genomic region in placental mammals
    Glazov, Evgeny A.
    McWilliam, Sean
    Barris, Wesley C.
    Dalrymple, Brian P.
    [J]. MOLECULAR BIOLOGY AND EVOLUTION, 2008, 25 (05) : 939 - 948
  • [10] Dendritic growth induced by BMP-7 requires Smad1 and proteasome activity
    Guo, X
    Lin, Y
    Horbinski, C
    Drahushuk, KM
    Kim, IJ
    Kaplan, PL
    Lein, P
    Wang, TW
    Higgins, D
    [J]. JOURNAL OF NEUROBIOLOGY, 2001, 48 (02): : 120 - 130