A MicroRNA feedback circuit in midbrain dopamine neurons.
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.
Kim
Jongpil
J
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.
Inoue
Keiichi
K
Ishii
Jennifer
J
Vanti
William B
WB
Voronov
Sergey V
SV
Murchison
Elizabeth
E
Hannon
Gregory
G
Abeliovich
Asa
A
D020413:3' Untranslated Regions / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D053595:Embryonic Stem Cells; D025461:Feedback, Physiological; D005260:Female; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008124:Locomotion; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D051381:Rats; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; D035683:MicroRNAs; D014157:Transcription Factors; C433629:homeobox protein PITX3; D043244:Ribonuclease III; D004298:Dopamine