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. 2025 Mar 6;33(3):566-582.e6.
doi: 10.1016/j.str.2024.12.019. Epub 2025 Jan 24.

Structures and mRNP remodeling mechanism of the TREX-2 complex

Yihu Xie  1 , Bradley P Clarke  2 , Dongqi Xie  3 , Menghan Mei  2 , Prasanna Bhat  3 , Pate S Hill  2 , Alexia E Angelos  2 , Tolga Çağatay  3 , Mariam Haider  4 , Scott E Collier  4 , Melissa G Chambers  4 , Vasilisa Aksenova  5 , Mary Dasso  5 , Beatriz M A Fontoura  3 , Yi Ren  6
Affiliations

Structures and mRNP remodeling mechanism of the TREX-2 complex

Yihu Xie et al. Structure. .

Abstract

mRNAs are packaged with proteins into messenger ribonucleoprotein complexes (mRNPs) in the nucleus. mRNP assembly and export are of fundamental importance for all eukaryotic gene expression. Before export to the cytoplasm, mRNPs undergo dynamic remodeling governed by the DEAD-box helicase DDX39B (yeast Sub2). DDX39B/Sub2 primarily functions in the nucleus and leaves the mRNP prior to export through the nuclear pore complex; however, the underlying mechanisms remain elusive. Here, we identify the conserved TREX-2 complex as the long-sought factor that facilitates DDX39B/Sub2 to complete the mRNP remodeling cycle. Our crystallographic and cryoelectron microscopy (cryo-EM) analyses demonstrate that TREX-2 modulates the activities of DDX39B/Sub2 through multiple interactions. Critically, a conserved "trigger loop" from TREX-2 splits the two RecA domains of DDX39B/Sub2 and promotes the removal of DDX39B/Sub2 from mRNP. Our findings suggest that TREX-2 coordinates with DDX39B/Sub2 and the human export receptor NXF1-NXT1 (yeast Mex67-Mtr2) to complete the final steps of nuclear mRNP assembly.

Keywords: DDX39B; DEAD-box ATPase; GANP; R-loop; Sub2; TREX; TREX-2; UAP56; mRNA nuclear export; mRNP remodeling.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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