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Science 31 August 2007:
Vol. 317. no. 5842, pp. 1220 - 1224
DOI: 10.1126/science.1140481
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Reports

A MicroRNA Feedback Circuit in Midbrain Dopamine Neurons

Jongpil Kim,1 Keiichi Inoue,1 Jennifer Ishii,1 William B. Vanti,1 Sergey V. Voronov,1 Elizabeth Murchison,2 Gregory Hannon,2 Asa Abeliovich1*

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.

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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