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Transcription profiling of mouse CAD cells transfected with miR-124a-2 reveals the microRNA miR-124 Promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing

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

ORGANISM(S): Mus musculus

SUBMITTER: Jiangwen Zhang

PROVIDER: E-GEOD-8498 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Project description: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

2007-08-04 | GSE8498 | GEO

Polypyrimidine Tract Binding Proteins PTBP1 and PTBP2 Interact with Distinct Proteins Under Splicing Conditions

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An Alternative Splicing Event Amplifies Evolutionary Differences Between Vertebrates

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2015-09-01 | E-GEOD-69656 | biostudies-arrayexpress

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2016-07-03 | E-GEOD-70985 | biostudies-arrayexpress

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2016-07-03 | E-GEOD-71075 | biostudies-arrayexpress

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2016-08-11 | E-MTAB-4847 | biostudies-arrayexpress

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Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention

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2012-07-12 | E-GEOD-37933 | biostudies-arrayexpress

Splicing analyses of mESCs, mNPCs, and mMNs

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2016-07-03 | E-GEOD-71079 | biostudies-arrayexpress

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