Dysregulation of AGO2-miRNA dynamics underlies the AGO2-associated Lessel-Kreienkamp syndrome [miRNA-Seq]

Mutations in human Argonaute genes, AGO1 and AGO2, are associated with neurodevelopmental disorders. Although multiple patients have been identified, the underlying molecular basis for pathogenesis remains unclear. Here, we performed an extensive investigation of five AGO2 mutations (p.L192P, p.A367P, p.T357M, p.F182del, and p.G733R) linked to different clinical severities. Primary mouse cortical neurons were transduced with AAVs to express EGFP-AGO2-WT or EGFP-AGO2-L192P and immunoprecipitation against EGFP was performed to enrich AGO2-bound miRNA for subsequent miRNA sequencing.