Mef2-mediated Transcription of the MiR379-410 Cluster Regulates Activity-dependent Dendritogenesis by Fine-tuning Pumilio2 Protein Levels

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2009 Feb 7

PMID 19197241

Citations 214

Authors

Roberto Fiore

Sharof Khudayberdiev

Mette Christensen

Gabriele Siegel

Steven W Flavell

Tae-Kyung Kim

Michael E Greenberg

Gerhard Schratt

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Involvement of extracellular vesicle microRNA clusters in developing healthy and Rett syndrome brain organoids.

Bahram Sangani N, Koetsier J, Gomes A, Diogo M, Fernandes T, Bouwman F Cell Mol Life Sci. 2024; 81(1):410.

PMID: 39305343 PMC: 11416455. DOI: 10.1007/s00018-024-05409-7.

FUS-dependent microRNA deregulations identify TRIB2 as a druggable target for ALS motor neurons.

Ho W, Chak L, Hor J, Liu F, Diaz-Garcia S, Chang J iScience. 2023; 26(11):108152.

PMID: 37920668 PMC: 10618709. DOI: 10.1016/j.isci.2023.108152.

Expression of microRNA-379 reduces metastatic spread of prostate cancer.

Cassidy J, Voss G, Underbjerg K, Persson M, Ceder Y Front Oncol. 2023; 13:1252915.

PMID: 37781173 PMC: 10539900. DOI: 10.3389/fonc.2023.1252915.

circ_0000018 downregulation peripherally ameliorates neuroprotection against acute ischemic stroke through the miR‑871/BCL2L11 axis.

Jiang M, Wang X, Jiang S Mol Med Rep. 2023; 28(5).

PMID: 37772397 PMC: 10568247. DOI: 10.3892/mmr.2023.13107.

The role of microRNAs in neurobiology and pathophysiology of the hippocampus.

Rashidi S, Kalirad A, Rafie S, Behzad E, Dezfouli M Front Mol Neurosci. 2023; 16:1226413.

PMID: 37727513 PMC: 10506409. DOI: 10.3389/fnmol.2023.1226413.

References

Turrigiano G . Homeostatic signaling: the positive side of negative feedback. Curr Opin Neurobiol. 2007; 17(3):318-24. DOI: 10.1016/j.conb.2007.04.004. View

Vo N, Klein M, Varlamova O, Keller D, Yamamoto T, Goodman R . A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc Natl Acad Sci U S A. 2005; 102(45):16426-31. PMC: 1283476. DOI: 10.1073/pnas.0508448102. View

Hong E, West A, Greenberg M . Transcriptional control of cognitive development. Curr Opin Neurobiol. 2005; 15(1):21-8. DOI: 10.1016/j.conb.2005.01.002. View

Stark K, Xu B, Bagchi A, Lai W, Liu H, Hsu R . Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat Genet. 2008; 40(6):751-60. DOI: 10.1038/ng.138. View

Flavell S, Cowan C, Kim T, Greer P, Lin Y, Paradis S . Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science. 2006; 311(5763):1008-12. DOI: 10.1126/science.1122511. View

Chen G, Li W, Zhang Q, Regulski M, Sinha N, Barditch J . Identification of synaptic targets of Drosophila pumilio. PLoS Comput Biol. 2008; 4(2):e1000026. PMC: 2265480. DOI: 10.1371/journal.pcbi.1000026. View

Seitz H, Royo H, Bortolin M, Lin S, Ferguson-Smith A, Cavaille J . A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Res. 2004; 14(9):1741-8. PMC: 515320. DOI: 10.1101/gr.2743304. View

Sutton M, Schuman E . Dendritic protein synthesis, synaptic plasticity, and memory. Cell. 2006; 127(1):49-58. DOI: 10.1016/j.cell.2006.09.014. View

Calabresi P, Picconi B, Tozzi A, Di Filippo M . Dopamine-mediated regulation of corticostriatal synaptic plasticity. Trends Neurosci. 2007; 30(5):211-9. DOI: 10.1016/j.tins.2007.03.001. View

10.

Flavell S, Greenberg M . Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system. Annu Rev Neurosci. 2008; 31:563-90. PMC: 2728073. DOI: 10.1146/annurev.neuro.31.060407.125631. View

11.

Kiebler M, Bassell G . Neuronal RNA granules: movers and makers. Neuron. 2006; 51(6):685-90. DOI: 10.1016/j.neuron.2006.08.021. View

12.

Chen Y, Ghosh A . Regulation of dendritic development by neuronal activity. J Neurobiol. 2005; 64(1):4-10. DOI: 10.1002/neu.20150. View

13.

Tsang J, Zhu J, van Oudenaarden A . MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Mol Cell. 2007; 26(5):753-67. PMC: 2072999. DOI: 10.1016/j.molcel.2007.05.018. View

14.

Guo X, Lin Y, Horbinski C, Drahushuk K, Kim I, KAPLAN P . Dendritic growth induced by BMP-7 requires Smad1 and proteasome activity. J Neurobiol. 2001; 48(2):120-30. View

15.

Waites C, Craig A, Garner C . Mechanisms of vertebrate synaptogenesis. Annu Rev Neurosci. 2005; 28:251-74. DOI: 10.1146/annurev.neuro.27.070203.144336. View

16.

Glazov E, McWilliam S, Barris W, Dalrymple B . Origin, evolution, and biological role of miRNA cluster in DLK-DIO3 genomic region in placental mammals. Mol Biol Evol. 2008; 25(5):939-48. DOI: 10.1093/molbev/msn045. View

17.

Sandelin A, Alkema W, Engstrom P, Wasserman W, Lenhard B . JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Res. 2003; 32(Database issue):D91-4. PMC: 308747. DOI: 10.1093/nar/gkh012. View

18.

Steward O . mRNA at synapses, synaptic plasticity, and memory consolidation. Neuron. 2002; 36(3):338-40. DOI: 10.1016/s0896-6273(02)01006-1. View

19.

Ye B, Petritsch C, Clark I, Gavis E, Jan L, Jan Y . Nanos and Pumilio are essential for dendrite morphogenesis in Drosophila peripheral neurons. Curr Biol. 2004; 14(4):314-21. DOI: 10.1016/j.cub.2004.01.052. View

20.

Siegel G, Obernosterer G, Fiore R, Oehmen M, Bicker S, Christensen M . A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nat Cell Biol. 2009; 11(6):705-16. PMC: 3595613. DOI: 10.1038/ncb1876. View