New insights into the formation of active nonsensemediated decay complexes

In the nonsense-mediated mRNA decay (NMD) pathway, an exon-junction protein complex (EJC) and hUpf proteins mediate rapid downregulation of aberrant mRNAs that terminate translation upstream of the last splice junction. Two EJC subunits, Y14 and RNPS1, have been proposed to act as a link between splicing and NMD by recruiting hUpf3 and the other hUpf proteins. New studies now present evidence that Y14 is directly involved in NMD, and that Y14 is required for hUpf3 activity. These findings suggest unforeseen intricacies in the formation of active NMD complexes.