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-Structure paper
| タイトル | Molecular basis of polyadenylated RNA fate determination in the nucleus. |
|---|---|
| ジャーナル・号・ページ | Nature, Vol. 655, Issue 8124, Page 1070-1078, Year 2026 |
| 掲載日 | 2026年6月17日 |
著者 | Andrii Bugai / Ulrich Hohmann / Ana Lorenzo / Max Graf / Laura Fin / Jérôme O Rouvière / Laszlo Tirian / Yuhui Dou / Marion Le Rest / Patrik Polák / Dennis Johnsen / Lis Jakobsen / Jens Skorstengaard Andersen / Julius Brennecke / Clemens Plaschka / Torben Heick Jensen / ![]() |
| PubMed 要旨 | Eukaryotic genomes generate a plethora of polyadenylated (pA) RNAs, which are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA RNPs, including ...Eukaryotic genomes generate a plethora of polyadenylated (pA) RNAs, 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 nucleus. 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-2, which triggers transcript release from UAP56 to facilitate export. Here we reveal that the poly(A) tail exosome targeting (PAXT) connection 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. |
リンク | Nature / PubMed:42310446 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.62 - 6.2 Å |
| 構造データ | EMDB-54282, PDB-9rv1: ![]() EMDB-54283: Human UAP56-RNA - SAC3D1-PCID2-SEM1 complex, Map A ![]() EMDB-54284: Map B of the human UAP56-RNA - SAC3D1-PCID2-SEM1 complex EMDB-56930, PDB-28wy: EMDB-56931, PDB-28wz: EMDB-56932, PDB-28xa: EMDB-56933, PDB-28xb: |
| 化合物 | ![]() ChemComp-ANP: ![]() ChemComp-MG: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | GENE REGULATION / mRNA export |
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