Abstract

The nuclear export of messenger RNA mRNA is a key step in eukaryotic gene expression. Despite recent insights into the nuclear packaging of human mRNAs into ribonucleoprotein complexes (mRNPs), the subsequent molecular events that govern mRNA export are poorly understood. Here, I will present our recent structural, biochemical, and genetic data on how human mRNAs are prepared for their nuclear export and quality controlled. This pathway involves the recognition and remodeling of mRNPs by the transcription-export complexes (TREX), the formation of export-competent mRNPs, the docking of mRNPs at the nuclear pore complex (NPC), and the release of mRNPs at the NPC to initiate export. Our biochemical and structural data uncover the ATPase DDX39 /UAP56 as a central molecular switch that directs mRNPs through TREX and the NPC -anchored TREX -2 complex using its ATPase and mRNA-binding cycle. Finally, we discover a paralogous complex to TREX -2, which directs mRNPs towards decay instead of export. Our combined findings provide insights into the packaging and export of mRNA and its quality control.