Post-transcriptional Regulation of α-Synuclein Expression by mir-7 and mir-153

Genetic and biochemical studies have established a central role for α-synuclein accumulation in the pathogenesis of Parkinson disease. Here, two microRNAs, namely mir-7 and mir-153, have been identified to regulate α-synuclein levels post-transcriptionally. These microRNAs bind specifically to the 3′-untranslated region of α-synuclein and down-regulate its mRNA and protein levels, with their effect being additive. They are expressed predominantly in the brain with a pattern that mirrors synuclein expression in different tissues as well as during neuronal development, indicating that they play a tuning role in the amount of α-synuclein produced. Overexpression of mir-7 and mir-153 significantly reduces endogenous α-synuclein levels, whereas inhibition of mir-7 and mir-153 enhances translation of a luciferase construct bearing the α-synuclein 3′-untranslated region in primary neurons. These findings reveal a significant additional mechanism by which α-synuclein is regulated and point toward new therapeutic regimes for lowering endogenous α-synuclein levels in patients with familial or sporadic Parkinson disease.

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