Ribosome occupancy and miRNA-mediated silencing of upregulated genes in attention deficit hyperactivity disorder

This study investigates the regulatory role of microRNAs (miRNAs) in suppressing the overexpression of genes associated with Attention-Deficit Hyperactivity Disorder (ADHD), a genetically influenced neurodevelopmental disorder. A computational framework based on the 7mer-m8 seed match model was used to predict miRNA interactions with nine upregulated genes, aiming to identify miRNAs capable of binding to their coding sequences (CDS) and regulating gene expression.

Coding sequences were retrieved from NCBI and analyzed for miRNA binding sites using established bioinformatics tools. Multiple miRNAs were found to target individual genes, including 36 for CHRNA4 and 17 for ADRA2C. Key parameters-such as GC and GC3 content, AMFE, COSM, translational frequency, RNA editing, mRNA stability, and ribosome residence time (RRT)-were assessed. Results indicated high GC (59.2 %) and GC3 (75.0 %) content at target regions, favoring miRNA binding. Notably, miR-4488 targeted the ADRA2C gene at two CDS positions (734-751 and 820-837). High RRT values (e.g., 1.17 for ADRA2C) and low compAI scores suggested slow translation and effective gene repression by miRNAs.

The study concludes that specific miRNAs can bind within the CDS of overexpressed genes in ADHD, potentially suppressing their translation. These findings support the therapeutic potential of miRNAs in regulating gene expression in ADHD and lay the groundwork for future research on miRNA-based interventions in neurodevelopmental disorders.