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| Status |
Public on Aug 04, 2007 |
| Title |
The MicroRNA miR-124 Promotes Neuronal Differentiation by Triggering Brain-Specific Alternative Pre-mRNA Splicing |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Both microRNAs and alternative pre-mRNA splicing have been implicated in the development of the nervous system (NS), but functional interactions between these two pathways are poorly understood. We demonstrate that the neuron-specific microRNA miR-124a directly targets PTBP1/PTB/hnRNPI mRNA, which encodes a global repressor of alternative pre-mRNA splicing in non-neuronal cells. Among the targets of PTBP1 is a critical cassette exon in the pre-mRNA of PTBP2/nPTB/brPTB, an NS-enriched PTBP1 homolog. When this exon is skipped, PTBP2 mRNA is subject to nonsense-mediated decay. During neuronal differentiation, miR-124a reduces PTBP1 levels leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. These events culminate in the transition from non-NS to NS-specific alternative splicing patterns. We also present evidence that miR-124a plays a key role in the differentiation of progenitor cells to mature neurons. Thus, miR-124a promotes NS development at least in part by regulating an intricate network of NS-specific alternative splicing.
We used microarrays to detail the global programme of gene expression of CAD cells over-expressing miR-124a-2.
Keywords: treatment versus control
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| |
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| Overall design |
Expression data from CAD cells transfected with plasmid expressing miR-124a-2.
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| |
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| Contributor(s) |
Makeyev EV, Zhang J, Carrasco M, Maniatis T |
| Citation(s) |
17679093 |
| Submission date |
Jul 16, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Jiangwen Zhang |
| E-mail(s) |
jzhang@cgr.harvard.edu
|
| Organization name |
Harvard University
|
| Department |
FAS Center for Systems Biology
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| Street address |
7 Divinity Ave
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02138 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA101601 |
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