8PNT

Structure of the human nuclear cap-binding complex bound to PHAX and m7G-capped RNA

Summary for 8PNT

• Entry DOI: 10.2210/pdb8pnt/pdb
• EMDB information: 17784
• Descriptor: Nuclear cap-binding protein subunit 1, Nuclear cap-binding protein subunit 2, Phosphorylated adapter RNA export protein, ... (4 entities in total)
• Functional Keywords: nuclear cap-binding complex, phax, pol ii transcript metabolism, rna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 197286.44

Authors

Dubiez, E.,Pellegrini, E.,Foucher, A.E.,Cusack, S.,Kadlec, J. (deposition date: 2023-07-01, release date: 2024-01-17)

Primary citation

Dubiez, E.,Pellegrini, E.,Finderup Brask, M.,Garland, W.,Foucher, A.E.,Huard, K.,Heick Jensen, T.,Cusack, S.,Kadlec, J.
Structural basis for competitive binding of productive and degradative co-transcriptional effectors to the nuclear cap-binding complex.
Cell Rep, 43:113639-113639, 2024

PubMed Abstract: The nuclear cap-binding complex (CBC) coordinates co-transcriptional maturation, transport, or degradation of nascent RNA polymerase II (Pol II) transcripts. CBC with its partner ARS2 forms mutually exclusive complexes with diverse "effectors" that promote either productive or destructive outcomes. Combining AlphaFold predictions with structural and biochemical validation, we show how effectors NCBP3, NELF-E, ARS2, PHAX, and ZC3H18 form competing binary complexes with CBC and how PHAX, NCBP3, ZC3H18, and other effectors compete for binding to ARS2. In ternary CBC-ARS2 complexes with PHAX, NCBP3, or ZC3H18, ARS2 is responsible for the initial effector recruitment but inhibits their direct binding to the CBC. We show that in vivo ZC3H18 binding to both CBC and ARS2 is required for nuclear RNA degradation. We propose that recruitment of PHAX to CBC-ARS2 can lead, with appropriate cues, to competitive displacement of ARS2 and ZC3H18 from the CBC, thus promoting a productive rather than a degradative RNA fate.

PubMed: 38175753
DOI: 10.1016/j.celrep.2023.113639

Experimental method

ELECTRON MICROSCOPY (3.46 Å)