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TitleMolecular insights into mRNA export regulation by the human TREX-2 complex.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateFeb 26, 2026
AuthorsXing Gong / Ran Tao / Xiaofei Ge / Huihui Zhu / Mengqi Li / Yufang Chen / Yongxiang Gao / Jing Hang / Xiaofeng Zhang /
PubMed AbstractThe nuclear export of mRNA represents a critical regulatory node in eukaryotic gene expression. This process is orchestrated by two conserved multi-subunit assemblies: the transcription-and-export ...The nuclear export of mRNA represents a critical regulatory node in eukaryotic gene expression. This process is orchestrated by two conserved multi-subunit assemblies: the transcription-and-export complex (TREX) and TREX-2. While TREX facilitates mRNP packaging through multivalent RNA-protein interactions, the precise mechanism by which TREX-2 contributes to mRNA export has remained elusive. Here, we report a functional interaction between UAP56 and TREX-2 and resolve the structures of TREX-2 in both apo and UAP56-bound states. UAP56 engages TREX-2 via its N-terminal region, positioning its RecA domains on the V-shaped surface of the complex. A conserved loop from TREX-2 inserts between the RecA domains of UAP56, stabilizing an open conformation. Biochemical assays demonstrate that TREX-2 significantly stimulates the ATPase activity of UAP56, thereby promoting RNA release. These findings provide structural and mechanistic insights into TREX-2-mediated regulation of mRNA export through UAP56 remodeling.
External linksNat Commun / PubMed:41748650 / PubMed Central
MethodsEM (single particle)
Resolution3.14 - 3.41 Å
Structure data

64390

9upb

EMDB-64390, PDB-9upb:
Structure of the human TREX-2 bound to UAP56
Method: EM (single particle) / Resolution: 3.41 Å

64391

9upc

EMDB-64391, PDB-9upc:
Structure of human TREX-2
Method: EM (single particle) / Resolution: 3.14 Å

Chemicals

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
KeywordsGENE REGULATION / mRNA nuclear export / TREX-2 / UAP56

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