期刊
MOLECULAR CELL
卷 27, 期 3, 页码 435-448出版社
CELL PRESS
DOI: 10.1016/j.molcel.2007.07.015
关键词
-
资金
- NINDS NIH HHS [2R01 NS 043915-27, R01 NS043915, R01 NS043915-27] Funding Source: Medline
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 1) mRNA, which encodes a global repressor of alternative premRNA 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 (NIVID). During neuronal differentiation, miR124 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.
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