奥地利维也纳生物中心Clemens Plaschka小组在研究中取得进展。他们提出了ATP门控分子开关协调人类信使RNA输出。相关论文于2025年11月6日发表在《自然》杂志上。

课题组揭示了人类mRNA输出关键事件的分子基础，包括mRNA结合的转录输出复合物（TREX）的重塑、输出能力mRNA的形成、mRNA在核孔复合物（NPC）的对接以及mRNA在NPC的释放以启动其输出。他们的生化和结构数据表明，ATP酶DDX39/UAP56作为一个中心分子开关，通过ATP门控的mRNA结合周期，将核质mRNA从TREX引导到NPC锚定的TREX-2复合物。总的来说，这些发现为一般和进化上保守的mRNA输出途径建立了一个机制框架。

据介绍，信使RNA （mRNA）的核输出是真核生物基因表达的重要步骤。尽管最近对新转录的mRNA如何被包装成核糖核蛋白复合物（mRNPs）有了深入的了解，但控制mRNA输出的后续事件却知之甚少。

附：英文原文

Title: An ATP-gated molecular switch orchestrates human messenger RNA export

Author: Hohmann, Ulrich, Graf, Max, Tirin, Lszl, Pacheco-Fiallos, Beln, Schellhaas, Ulla, Fin, Laura, Handler, Dominik, Philipps, Alex W., Riabov-Bassat, Daria, Faraway, Rupert W., Phringer, Thomas, Szalay, Michael-Florian, Roitinger, Elisabeth, Brennecke, Julius, Plaschka, Clemens

Issue&Volume: 2025-11-06

Abstract: The nuclear export of messenger RNA (mRNA) is an important step in eukaryotic gene expression1. Despite recent molecular insights into how newly transcribed mRNAs are packaged into ribonucleoprotein complexes (mRNPs)2,3, the subsequent events that govern mRNA export are poorly understood. Here, we uncover the molecular basis underlying key events of human mRNA export, including the remodeling of mRNP-bound transcription-export complexes (TREX), the formation of export-competent mRNPs, the docking of mRNPs at the nuclear pore complex (NPC), and the release of mRNPs at the NPC to initiate their export. Our biochemical and structural data show that the ATPase DDX39/UAP56 acts as a central molecular switch that directs nucleoplasmic mRNPs from TREX to NPC-anchored TREX-2 complexes through its ATP-gated mRNA-binding cycle. Collectively, these findings establish a mechanistic framework for a general and evolutionarily conserved mRNA export pathway.

DOI: 10.1038/s41586-025-09832-z

Source: https://www.nature.com/articles/s41586-025-09832-z