Structures and mRNP remodeling mechanism of the TREX-2 complex

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Structure Pub Date : 2025-01-24 DOI:10.1016/j.str.2024.12.019

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

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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.

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来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.