Objective
Recent studies suggest that ALS development may be driven by dysregulation of microRNAs, small RNA molecules that impact gene expression in a reversible manner. As microRNA biogenesis involves trans-activation response element DNA/RNA-binding protein of 43 kDa (TDP43), a protein with pathological links to ALS, we sought to identify particular microRNAs that interact with TDP43 to gain insight into relevant disease pathways, potential biomarkers, and reversible treatment targets for ALS.
Conclusion
Our findings demonstrated that TDP43 exhibits differential binding affinity for select microRNAs, and using cell models expressing TDP43 variants and microRNA profiling analyses, we further identified 65 microRNAs that differentially associated with TDP43 in our models. The hits included both novel microRNAs and microRNAs previously associated with ALS that potentially regulate predicted genes and pathways that may be important for disease pathogenesis.