title: miR-27b shapes the presynaptic transcriptome and influences neurotransmission by silencing the polycomb group protein Bmi1.
abstract: MicroRNAs (miRNAs) are short non-coding RNAs that are emerging as important post-transcriptional regulators of neuronal and synaptic development. The precise impact of miRNAs on presynaptic function and neurotransmission remains, however, poorly understood.
  
  
  
  Here, we identify miR-27b-an abundant neuronal miRNA implicated in neurological disorders-as a global regulator of the presynaptic transcriptome. miR-27b influences the expression of three quarters of genes associated with presynaptic function in cortical neurons. Contrary to expectation, a large majority of these genes are up-regulated by miR-27b. This stimulatory effect is mediated by miR-27b-directed silencing of several transcriptional repressors that cooperate to suppress the presynaptic transcriptome. The strongest repressive activity appears to be mediated by Bmi1, a component of the polycomb repressive complex implicated in self-renewal of neural stem cells. miR-27b knockdown leads to reduced synaptogenesis and to a marked decrease in neural network activity, which is fully restored by RNAi-mediated silencing of Bmi1.
  
  
  
  We conclude that silencing of Bmi1 by miR-27b relieves repression of the presynaptic transcriptome and supports neurotransmission in cortical networks. These results expand the repressive activity of Bmi1 to genes involved in synaptic function and identify a unique post-transcriptional circuitry that stimulates expression of synaptic genes and promotes synapse differentiation.
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
authors.forename: Vivian Y
authors.initials: VY
authors.lastname: Poon
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
authors.forename: Minxia
authors.initials: M
authors.lastname: Gu
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
authors.forename: Fang
authors.initials: F
authors.lastname: Ji
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
authors.forename: Antonius M
authors.initials: AM
authors.lastname: VanDongen
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore. marc.fivaz@duke-nus.edu.sg.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. marc.fivaz@duke-nus.edu.sg.
authors.forename: Marc
authors.identifier: 0000-0003-1003-7934
authors.initials: M
authors.lastname: Fivaz
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009434:Neural Pathways; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*; D017729:Presynaptic Terminals / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics; D055751:SOXC Transcription Factors / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics*; D059467:Transcriptome
chemical_list: C489421:Bmi1 protein, mouse; D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D055751:SOXC Transcription Factors; C490793:Sox11 protein, mouse; C096823:Zfp90 protein, mouse; D063150:Polycomb Repressive Complex 1
keywords: Epigenetics; Neurotransmission; Polycomb Group Protein; Synapse; Transcriptome; miRNAs