Figure 3.

From genes to disease and points of therapeutic intervention. Mutations in genes that participate in translation that alter global rates of ‐1 PRF elicit downstream post‐transcriptional surveillance pathways e.g. NMD that alter the transcriptome. This leads to altered gene expression (proteomic changes) and progression to disease states. Therapeutic approaches may include use of synthetic polynucleotide analogs (miRNAs and related derivitives) targeting specific ‐1 PRF signals designed to fine tune frameshifting rates. Given the epistatic relationship of NMD to ‐1 PRF, targeting this pathway using small molecule inhibitors presents another therapeutic modality.