28XB

Cryo-EM structure of the human UAP56-RNA - LENG8-PCID2-SEM1 complex

This is a non-PDB format compatible entry.

Summary for 28XB

• Entry DOI: 10.2210/pdb28xb/pdb
• EMDB information: 56933
• Descriptor: Maltose/maltodextrin-binding periplasmic protein,Leukocyte receptor cluster member 8,Leukocyte receptor cluster member 8,Leukocyte receptor cluster member 8,Leukocyte receptor cluster member 8, PCI domain-containing protein 2, 26S proteasome complex subunit SEM1, ... (5 entities in total)
• Functional Keywords: mrna export, gene regulation
• Biological source: Escherichia coli; More
• Total number of polymer chains: 5
• Total formula weight: 185211.08

Authors

Hohmann, U.,Graf, M.,Plaschka, C. (deposition date: 2026-02-25, release date: 2026-06-24, Last modification date: 2026-07-01)

Primary citation

Bugai, A.,Hohmann, U.,Lorenzo, A.,Graf, M.,Fin, L.,Rouviere, J.O.,Tirian, L.,Dou, Y.,Le Rest, M.,Polak, P.,Johnsen, D.,Jakobsen, L.,Andersen, J.S.,Brennecke, J.,Plaschka, C.,Jensen, T.H.
Molecular basis of polyadenylated RNA fate determination in the nucleus.
Nature, 2026

PubMed Abstract: 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.

PubMed: 42310446
DOI: 10.1038/s41586-026-10650-0

Experimental method

ELECTRON MICROSCOPY (6.2 Å)