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miR-27b shapes the presynaptic transcriptome and influences neurotransmission by silencing the polycomb group protein Bmi1
- Source :
- BMC Genomics
- Publication Year :
- 2016
-
Abstract
- Background 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. Results 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. Conclusions 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. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3139-7) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Synaptogenesis
Presynaptic Terminals
macromolecular substances
Neurotransmission
Biology
Synaptic Transmission
Polycomb Group Protein
SOXC Transcription Factors
Transcriptome
Synapse
03 medical and health sciences
Mice
RNA interference
Proto-Oncogene Proteins
microRNA
Neural Pathways
Genetics
Gene silencing
Animals
Cluster Analysis
Gene Silencing
RNA, Messenger
Polycomb Repressive Complex 1
Gene Expression Profiling
Cell biology
Rats
Gene Expression Regulation, Neoplastic
Repressor Proteins
MicroRNAs
030104 developmental biology
BMI1
miRNAs
RNA Interference
Epigenetics
Biotechnology
Research Article
Subjects
Details
- ISSN :
- 14712164
- Volume :
- 17
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC genomics
- Accession number :
- edsair.doi.dedup.....0b16ca63e8caf01d876ed56be2dc550d