9T3X

cryo-EM structure of CPSF160-WDR33-ZC3H18

Summary for 9T3X

• Entry DOI: 10.2210/pdb9t3x/pdb
• EMDB information: 55519
• Descriptor: Cleavage and polyadenylation specificity factor subunit 1, pre-mRNA 3' end processing protein WDR33, Maltose/maltodextrin-binding periplasmic protein,Zinc finger CCCH domain-containing protein 18 (3 entities in total)
• Functional Keywords: zc3h18, cpsf160, wdr33, complex, rna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 265185.02

Authors

Kuhn, C.C.,Chand, M.K.,Todesca, S.,Williams, K.,Keidel, A.,Garland, W.,Jensen, T.H.,Conti, E. (deposition date: 2025-10-30, release date: 2026-01-28, Last modification date: 2026-02-25)

Primary citation

Kuhn, C.C.,Chand, M.K.,Todesca, S.,Williams, K.,Keidel, A.,Garland, W.,Jensen, T.H.,Conti, E.
Direct coupling of the human nuclear exosome adaptors NEXT and PAXT with transcription termination and processing machineries.
Nucleic Acids Res., 54:-, 2026

PubMed Abstract: In human cells, the Nuclear EXosome Targeting (NEXT) and Poly(A) tail eXosome Targeting (PAXT) adaptors direct the nuclear exosome to degrade prematurely terminated RNA Polymerase II (Pol II) transcripts, ensuring nuclear RNA quality control. How these adaptors interact with transcription termination machineries remains largely unclear. Here, we leveraged in silico structure predictions of protein complexes to identify and model previously unreported interactions of NEXT- and PAXT-associated components with two transcription termination and processing machineries, the Integrator and Cleavage and Polyadenylation (CPA) complexes. Our computational models were validated through complementary in vitro biochemical approaches and single-particle cryo-EM analyses. We show that the ZC3H18 protein uses two different domains to directly recognize the INTS9/11 endonuclease module of Integrator and the mammalian Polyadenylation Specificity Factor (mPSF), a core CPA component. In turn, ZC3H18 can directly bind the scaffolding subunits of NEXT and PAXT via mutually exclusive interactions. Furthermore, we provide evidence that accessory PAXT components can be directly integrated with the mPSF core, establishing configurations that are mutually exclusive with those of canonical CPA subunits. These findings reveal a versatile interaction network capable of forming alternative structural frameworks linking transcription termination with nuclear RNA quality control.

PubMed: 41641703
DOI: 10.1093/nar/gkag088

Experimental method

ELECTRON MICROSCOPY (2.1 Å)