Abstract: Robustness in biological systems relies on quality control. While errors in the DNA are repaired to maintain fidelity in the flow of genetic information, errors in mRNA are dealt with by degrading the erroneous molecules via surveillance processes such as nonsense-mediated mRNA decay (NMD). Though all mRNAs degraded by NMD follow a set of canonical rules, the converse – that every mRNA that follows the rule is subject to NMD – is not true. The long-term goal of our research program is to understand the molecular logic governing the varying efficiency in RNA quality control and its impact on gene expression, and in turn, cellular phenotypes. In this talk, I will share our findings from investigating the cause and consequence of NMD inhibition in human skeletal muscle by the myopathic transcription factor, DUX4.