Unknown

Dataset Information

0

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-124 directly targets PTBP1 (PTB/hnRNP I) mRNA, which encodes a global repressor of alternative pre-mRNA splicing in nonneuronal cells. Among the targets of PTBP1 is a critical cassette exon in the pre-mRNA of PTBP2 (nPTB/brPTB/PTBLP), an NS-enriched PTBP1 homolog. When this exon is skipped, PTBP2 mRNA is subject to nonsense-mediated decay (NMD). During neuronal differentiation, miR-124 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-124 plays a key role in the differentiation of progenitor cells to mature neurons. Thus, miR-124 promotes NS development, at least in part by regulating an intricate network of NS-specific alternative splicing.

SUBMITTER: Makeyev EV 

PROVIDER: S-EPMC3139456 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing.

Makeyev Eugene V EV   Zhang Jiangwen J   Carrasco Monica A MA   Maniatis Tom T  

Molecular cell 20070801 3


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-124 directly targets PTBP1 (PTB/hnRNP I) mRNA, which encodes a global repressor of alternative pre-mRNA splicing in nonneuronal cells. Among the targets of PTBP1 is a critical cassette exon in the pre-mRNA of PTBP2 (nPTB/brPTB/PTBLP), an NS-enriched PT  ...[more]

Similar Datasets

2007-08-04 | GSE8498 | GEO
2008-06-16 | E-GEOD-8498 | biostudies-arrayexpress
| S-EPMC2702206 | biostudies-literature
| S-EPMC7826280 | biostudies-literature
| S-EPMC10651857 | biostudies-literature
| S-EPMC4526142 | biostudies-literature
| S-EPMC6041894 | biostudies-literature
| S-EPMC3500379 | biostudies-literature
| S-EPMC2665233 | biostudies-literature
| S-EPMC3339278 | biostudies-literature