An ATP-gated molecular switch orchestrates human messenger RNA export

"Here, we uncover the molecular basis underlying key events of human mRNA export, including the remodeling of mRNP-bound 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 their export. Our biochemical and structural data show that the ATPase DDX39/UAP56 acts as a central molecular switch that directs nucleoplasmic mRNPs from TREX to NPC-anchored TREX-2 complexes through its ATP-gated mRNA-binding cycle."

"Despite recent molecular insights into how newly transcribed mRNAs are packaged into ribonucleoprotein complexes (mRNPs)2,3, the subsequent events that govern mRNA export are poorly understood. Here, we uncover the molecular basis underlying key events of human mRNA export, including the remodeling of mRNP-bound 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 their export."

mRNA nuclear export is essential for eukaryotic gene expression. Newly transcribed mRNAs are packaged into mRNPs, but the downstream events that enable export were unclear. The ATPase DDX39/UAP56 functions as a central molecular switch that, through an ATP-gated mRNA-binding cycle, directs nucleoplasmic mRNPs from TREX complexes to NPC-anchored TREX-2. Remodeling of TREX-bound mRNPs produces export-competent mRNPs that dock at the nuclear pore complex and are released to initiate export. Biochemical and structural evidence supports these mechanistic steps, indicating a general and evolutionarily conserved mRNA export pathway.

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