Direct coupling of the human nuclear exosome adaptors NEXT and PAXT with transcription termination and processing machineries.

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

SUBMITTER: Kuhn CC 

PROVIDER: S-EPMC12873606 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature