A microRNA feedback circuit in midbrain dopamine neurons
A microRNA feedback circuit in midbrain dopamine neurons
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DOI：
10.1126/science.1140481
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发表时间：
2007-08-31
期刊：
影响因子：
56.9
通讯作者：
Abeliovich, Asa
中科院分区：
文献类型：
--
作者：
Kim, Jongpil;Inoue, Keiichi;Abeliovich, Asa
MicroRNAs （miRNAs）是进化上保守的，18- 25个核苷酸的非蛋白质编码转录物，在发育过程中转录后调节基因表达。mirna也存在于有丝分裂后细胞中，如哺乳动物中枢神经系统的神经元，但其功能尚不清楚。我们研究了mirna在哺乳动物中脑多巴胺能神经元（DNs）中的作用。我们发现了一种miRNA miR-133b，它在帕金森病患者的中脑dn中特异性表达，并且在中脑组织中缺乏。miR-133b在一个负反馈回路中调节中脑DNs的成熟和功能，该回路包括配对样同源结构域转录因子Pitx3。我们提出这种反馈回路在多巴胺能行为（如运动）的微调中所起的作用。
MicroRNAs ( miRNAs) are evolutionarily conserved, 18- to 25- nucleotide, non-protein coding transcripts that posttranscriptionally regulate gene expression during development. miRNAs also occur in postmitotic cells, such as neurons in the mammalian central nervous system, but their function is less well characterized. We investigated the role of miRNAs in mammalian midbrain dopaminergic neurons ( DNs). We identified a miRNA, miR-133b, that is specifically expressed in midbrain DNs and is deficient in midbrain tissue from patients with Parkinson's disease. miR-133b regulates the maturation and function of midbrain DNs within a negative feedback circuit that includes the paired-like homeodomain transcription factor Pitx3. We propose a role for this feedback circuit in the fine-tuning of dopaminergic behaviors such as locomotion.