Two closely related human nuclear export factors utilize entirely distinct export pathways.

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Nuclear mRNA export is crucial for gene expression.
• The human protein TAP (NXF1) mediates mRNA export via its interaction with the nuclear pore complex (NPC).
• TAP utilizes a specific carboxy-terminal domain for NPC interaction.

Purpose of the Study:

• To investigate the mechanism of nuclear mRNA export by NXF3, a protein related to TAP.
• To determine if NXF3 utilizes a similar pathway to TAP for RNA export.
• To identify the functional domains and export pathway of NXF3.

Main Methods:

• Investigated NXF3's ability to export tethered RNA transcripts.
• Assessed NXF3's subcellular localization and nucleocytoplasmic shuttling.
• Identified the nuclear export signal (NES) in NXF3 using functional assays.
• Tested the effect of Crm1-specific inhibitors on NXF3-mediated RNA export.

Main Results:

• NXF3 lacks the carboxy-terminal domain found in TAP.
• NXF3 retains the ability to export tethered RNA and shuttle between nucleus and cytoplasm.
• NXF3 possesses a novel Crm1-dependent nuclear export signal.
• NXF3-dependent RNA export is inhibited by Crm1-specific inhibitors, unlike TAP function.

Conclusions:

• NXF3 mediates nuclear RNA export through a pathway distinct from TAP.
• NXF3 utilizes a Crm1-dependent export pathway, compensating for the absence of a direct NPC-binding domain.
• TAP and NXF3 represent related proteins employing unrelated mechanisms for nuclear mRNA export.