Structural basis for binding the TREX2 complex to nuclear pores, GAL1 localisation and mRNA export

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• The TREX2 complex is crucial for mRNA export and gene positioning at nuclear pore complexes (NPCs).
• Interaction with Nup1 is implicated in TREX2 function, but its precise role is unclear due to pleiotropic effects of Nup1 mutations.

Purpose of the Study:

• To elucidate the structural basis of the TREX2:Nup1 interaction at NPCs.
• To understand the functional significance of this interaction in mRNA export and gene regulation.

Main Methods:

• Determined the crystal structure of the Nup1:TREX2 interaction interface.
• Engineered a Sac3 variant to specifically disrupt NPC binding without affecting TREX2 assembly.
• Assessed the impact of the Sac3 variant on GAL1 gene positioning, mRNA export, and cell growth.

Main Results:

• Structural analysis revealed the Nup1:TREX2 binding interface.
• The engineered Sac3 variant impaired NPC association of GAL1 and inhibited bulk mRNA export.
• This variant also caused growth defects, confirming the functional importance of the TREX2:Nup1 interaction.

Conclusions:

• The TREX2:Nup1 interaction is essential for efficient bulk mRNA export.
• This interaction facilitates the repositioning of actively transcribed genes like GAL1 to NPCs for proper transcriptional control.
• NPC-bound Ulp1-mediated SUMO removal from repressors is linked to this process.