Biochemical analysis reveals AGO2 mutations alter miRNA dynamics in neurons, indicating potential neurodevelopmental consequences.
Key Points
AGO2 mutations result in altered miRNA dynamics and impaired target RNA release, contributing to neurodevelopmental pathology.
The L192P and A367P mutations exhibit prolonged target RNA dwell times, leading to mis-targeting of miRNAs and indicating dysfunctional protein behavior.
RNA Bind-n-Seq experiments highlight mis-targeting issues in AGO2 mutants, correlating with neurodevelopmental disorder symptoms in affected patients.
In vivo studies show that the p.L192P variant causes significantly altered breeding ability and disrupted cortical transcriptomes in mice.