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      A MicroRNA feedback circuit in midbrain dopamine neurons.

      Science (New York, N.Y.)

      3' Untranslated Regions, metabolism, Aged, Aged, 80 and over, Animals, Cell Differentiation, Cell Line, Cells, Cultured, Dopamine, Embryonic Stem Cells, Feedback, Physiological, Female, Gene Expression Regulation, Homeodomain Proteins, Humans, Locomotion, Male, Mesencephalon, cytology, Mice, MicroRNAs, Middle Aged, Models, Biological, Neurons, Parkinson Disease, Rats, Ribonuclease III, genetics, Transcription Factors, Transcription, Genetic

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          Abstract

          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.

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          Author and article information

          Journal
          17761882
          2782470
          10.1126/science.1140481

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