An ATP-gated molecular switch orchestrates human mRNA export

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Nuclear export of messenger RNA (mRNA) is crucial for eukaryotic gene expression.
• While mRNA packaging into ribonucleoprotein complexes (mRNPs) is understood, the export process remains unclear.

Purpose of the Study:

• To elucidate the molecular mechanisms governing human mRNA export.
• To identify key proteins and pathways involved in the transition from transcription to nuclear export.

Main Methods:

• Biochemical assays
• Structural biology techniques
• Analysis of transcription-export complexes (TREX) and nuclear pore complexes (NPCs)

Main Results:

• Identified the ATPase UAP56 (DDX39) as a central molecular switch in mRNA export.
• UAP56 directs nucleoplasmic mRNPs from TREX to NPC-anchored TREX-2 complexes via an ATP-gated mRNA-binding cycle.
• Detailed the remodeling of mRNP complexes, their docking at NPCs, and release for export.

Conclusions:

• Established a mechanistic framework for a general and evolutionarily conserved mRNA export pathway.
• The findings provide critical insights into the regulation of gene expression at the post-transcriptional level.