Molecular insights into mRNA export regulation by the human TREX-2 complex
Xing Gong1, Ran Tao1, Xiaofei Ge2
1Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, The USTC RNA Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
The TREX-2 complex interacts with UAP56, revealing its structure and function in mRNA export. This interaction stimulates UAP56
Area of Science:
- Molecular Biology
- Gene Expression Regulation
- Eukaryotic Cell Biology
Background:
- Nuclear export of messenger RNA (mRNA) is a key control point for gene expression in eukaryotes.
- Two main protein complexes, transcription-and-export (TREX) and TREX-2, manage mRNA export.
- The specific role of TREX-2 in mRNA export remained unclear.
Purpose of the Study:
- To elucidate the mechanism of TREX-2 in mRNA export.
- To investigate the interaction between UAP56 and TREX-2.
- To determine the structural basis of TREX-2 function.
Main Methods:
- X-ray crystallography to resolve TREX-2 structures (apo and UAP56-bound).
- Biochemical assays to assess UAP56 ATPase activity.
- Analysis of protein-protein interactions between UAP56 and TREX-2.
Main Results:
- A functional interaction between UAP56 and TREX-2 was identified.
- The structures of TREX-2, both alone and bound to UAP56, were determined.
- TREX-2 binding stabilizes an open conformation of UAP56 and enhances its RNA-release activity.
Conclusions:
- TREX-2 regulates mRNA export by remodeling UAP56.
- Structural and mechanistic insights into TREX-2-UAP56 interaction were provided.
- This study clarifies TREX-2's role in facilitating mRNA export.
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