The MicroRNA miR-124 Promotes Neuronal Differentiation by Triggering Brain-Specific Alternative Pre-mRNA Splicing

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PubMed ID: none
Contact: Jiangwen Zhang

Image:email_GSE8498.png
Harvard University

Species: Mus musculus
Platform: Affymetrix GeneChip Mouse Genome 430 2.0 Array
Number of Samples: 6
Date Range: 09/02/2005 - 10/14/2005
Experiment Quality: 99.14
2.85 %
Link to Repository: GSE8498
Original Intensity Data: Download
Clean Intensity Data: Download
Original PLIER Data: Download
Clean PLIER Data: Download
Clean CEL Files:
Data Rank:

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.

Design: Expression data from CAD cells transfected with plasmid expressing miR-124a-2.

Type: treatment versus control


Contents

[edit] Contributors

  • Eugene V Makeyev
  • Jiangwen Zhang
  • Monica Carrasco
  • Tom Maniatis

[edit] Protocols

[edit] References

[edit] Links

GEO Accession for this experiment: GSE8498. (Public on Aug 04 2007)

RAW data: tar file.

[edit] Analysis

[edit] Samples/Quality Control

Sample Date Scanned Source Link Probe Variance Data Artifact Mask Quality Score
CAD_C1 09/02/2005 12:58:33 GSM210755 Probe variance for  CAD_C1 Artifact mask for  CAD_C1 98.9156
1.14 %
CAD_C2 10/14/2005 10:59:39 GSM210756 Probe variance for  CAD_C2 Artifact mask for  CAD_C2 99.0495
0.12 %
CAD_C3 10/14/2005 11:08:52 GSM210757 Probe variance for  CAD_C3 Artifact mask for  CAD_C3 99.6166
0.03 %
CAD_T1 09/02/2005 11:21:26 GSM210758 Probe variance for  CAD_T1 Artifact mask for  CAD_T1 98.9572
0.29 %
CAD_T2 10/14/2005 11:18:02 GSM210759 Probe variance for  CAD_T2 Artifact mask for  CAD_T2 98.8458
15.40 %
CAD_T3 10/14/2005 11:27:12 GSM210760 Probe variance for  CAD_T3 Artifact mask for  CAD_T3 99.4345
0.14 %