A MicroRNA Feedback Circuit in Midbrain Dopamine Neurons

TLDR

MicroRNAs are conserved 18‑25‑nt non‑protein‑coding RNAs that regulate gene expression during development and are present in neurons, though their neuronal functions remain poorly understood. The study examined the role of miRNAs in mammalian midbrain dopaminergic neurons and proposed that a miR‑133b–Pitx3 feedback circuit fine‑tunes dopaminergic behaviors such as locomotion. miR‑133b, specifically expressed in midbrain dopaminergic neurons, is reduced in Parkinson’s disease tissue and regulates neuronal maturation and function through a negative feedback loop with the transcription factor Pitx3.

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.