Nonsense-mediated RNA decay (NMD), an mRNA quality control mechanism, triggers degradation of mRNAs that contain premature termination codon (PTC) within their coding regions. NMD is a relatively conservative process that involves many trans-acting factors. The key domains for their function in NMD are conserved in evolution. These trans-acting factors are classified as different groups by their function in NMD. In addition, the mRNP formation is dynamic in NMD process because of sequential recruitment and interaction of these factors. To gain an insight into the mechanism of NMD, we dissect the mechanism of NMD based on the information on the structure, the regulation and interaction of these factors.