奥尔胡斯大学Torben Heick Jensen团队的一项最新研究开发出细胞核中聚腺苷化RNA命运决定的分子基础。相关论文于2026年6月17日发表于国际顶尖学术期刊《自然》杂志上。

在这里，该课题组人员发现聚（A）尾外泌体靶向（PAXT）连接8结合TREX-2样模块，该模块从UAP56释放pA+ RNA，由核外泌体衰变。该模块的核心由LENG8-PCID2-SEM1三聚体组成，该三聚体在结构和生化上与TREX-2的中心GANP–PCID2–SEM1三聚体相当。突变和转录组学数据表明，pA+ RNPs的核命运是由核质PAXT和核孔复合物相关TREX-2的竞争作用决定的，它们分别将RNA结合的UAP56解释为RNA衰变或输出的信号。由于PAXT的RNA靶点通常较短且内含子较少，因此研究团队提出了一个pA+ RNP命运决定的整体模型，其中PAXT和TREX-2的不同亚核定位控制着短的非功能性pA+ RNA的降解，同时允许其较长且具有功能的对应物输出。

据悉，真核生物基因组产生过多的聚腺苷化（pA+）RNAs，它们被包装成核糖核蛋白颗粒（RNPs）。为了确保基因的忠实表达，功能pA+ RNPs，包括蛋白质编码RNPs，被输出到细胞质中，而非功能pA+ RNPs中的转录本在核胞中被降解。细胞如何区分这些相反的命运仍然未知。DExD-box ATPase UAP56（也称为DDX39B）是功能性pA+ RNPs的核心成分，并促进它们与核孔复合物锚定的TREX-2对接，从而触发UAP56的转录产物释放以促进输出。

附：英文原文

Title: Molecular basis of polyadenylated RNA fate determination in the nucleus

Author: Bugai, Andrii, Hohmann, Ulrich, Lorenzo, Ana, Graf, Max, Fin, Laura, Rouvire, Jrme O., Tirian, Laszlo, Dou, Yuhui, Le Rest, Marion, Polk, Patrik, Johnsen, Dennis, Jakobsen, Lis, Andersen, Jens Skorstengaard, Brennecke, Julius, Plaschka, Clemens, Jensen, Torben Heick

Issue&Volume: 2026-06-17

Abstract: Eukaryotic genomes generate a plethora of polyadenylated (pA+) RNAs1,2, which are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA+ RNPs, including protein-coding RNPs, are exported to the cytoplasm, whereas transcripts within non-functional pA+ RNPs are degraded in the nucleus1,2,3,4. How cells distinguish these opposing fates remains unknown. The DExD-box ATPase UAP56 (also known as DDX39B) is a central component of functional pA+ RNPs, and promotes their docking to the nuclear pore complex-anchored TREX-25,6, which triggers transcript release from UAP56 to facilitate export7. Here we reveal that the poly(A) tail exosome targeting (PAXT) connection8 binds a TREX-2-like module, which releases pA+ RNAs from UAP56 for decay by the nuclear exosome. The core of this module consists of a LENG8–PCID2–SEM1 trimer, which we show is structurally and biochemically equivalent to the central GANP–PCID2–SEM1 trimer of TREX-2. Mutagenesis and transcriptomic data demonstrate that the nuclear fate of pA+ RNPs is governed by the contending actions of nucleoplasmic PAXT and nuclear pore complex-associated TREX-2, which interpret RNA-bound UAP56 as a signal for RNA decay or export, respectively. As RNA targets of PAXT are generally short and intron-poor, we propose an overall model for pA+ RNP fate determination whereby the distinct sub-nuclear localizations of PAXT and TREX-2 govern the degradation of short non-functional pA+ RNAs while allowing export of their longer and functional counterparts.

DOI: 10.1038/s41586-026-10650-0

Source: https://www.nature.com/articles/s41586-026-10650-0

期刊信息

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504

官方网址：http://www.nature.com/

投稿链接：http://www.nature.com/authors/submit_manuscript.html