Structural insights into nonsense-mediated mRNA decay (NMD) by electron microscopy

Nonsense-mediated mRNA decay (NMD) is a pathway that detects and degrades mRNAs containing premature translation termination codons (PTCs). In humans, recognition of these aberrant mRNAs requires an exon-junction-complex (EJC) placed downstream of a PTC and the dynamic interaction of several UPF/SMG proteins, the ribosome and the EJC. These interactions promote UPF1 phosphorylation by SMG1 kinase, triggering mRNA degradation. Recent progress in our understanding of NMD has been achieved by combining cryo-electron microscopy, high-resolution structures, interaction data and functional assays. These studies uncovered a mechanism regulating SMG1 kinase as well as the architecture and functional implications of a complex containing UPF1, UPF2, UPF3 and EJC. Collectively these findings reveal the role of protein scaffolds and conformational changes in NMD regulation.