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A MicroRNA Feedback Circuit in Midbrain Dopamine Neurons
Jongpil Kim,1Keiichi Inoue,1Jennifer Ishii,1William B. Vanti,1Sergey V. Voronov,1Elizabeth Murchison,2Gregory Hannon,2Asa Abeliovich1*
MicroRNAs (miRNAs) are evolutionarily conserved, 18- to 25-nucleotide,non–protein coding transcripts that posttranscriptionallyregulate gene expression during development. miRNAs also occurin postmitotic cells, such as neurons in the mammalian centralnervous system, but their function is less well characterized.We investigated the role of miRNAs in mammalian midbrain dopaminergicneurons (DNs). We identified a miRNA, miR-133b, that is specificallyexpressed in midbrain DNs and is deficient in midbrain tissuefrom patients with Parkinson's disease. miR-133b regulates thematuration and function of midbrain DNs within a negative feedbackcircuit that includes the paired-like homeodomain transcriptionfactor Pitx3. We propose a role for this feedback circuit inthe fine-tuning of dopaminergic behaviors such as locomotion.
1 Departments of Pathology and Neurology, Center for Neurobiology and Behavior, and Taub Institute, Columbia University, College of Physicians and Surgeons 15-403, 630 West 168th Street, New York, NY 10032, USA. 2 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
* To whom correspondence should be addressed. E-mail: aa900{at}columbia.edu
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