9T5J

RPAP2-GPN1-GPN3 complex (GDP-bound)

Summary for 9T5J

• Entry DOI: 10.2210/pdb9t5j/pdb
• EMDB information: 55585
• Descriptor: Putative RNA polymerase II subunit B1 CTD phosphatase RPAP2, GPN-loop GTPase 1, GPN-loop GTPase 3, ... (5 entities in total)
• Functional Keywords: cytoplasm, polymerase, biogenesis, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 145428.37

Authors

Hlavata, A.,Bernecky, C. (deposition date: 2025-11-05, release date: 2026-07-15, Last modification date: 2026-07-22)

Primary citation

Hlavata, A.,Neuditschko, B.,Schellhaas, U.,Plaschka, C.,Herzog, F.,Bernecky, C.
Structure of cytoplasmic RNA polymerase II.
Nat Commun, 2026

PubMed Abstract: RNA polymerase II (Pol II) must be assembled in the cytoplasm before it enters the nucleus, where it transcribes protein-coding genes. Although transcription by Pol II is intensively studied, how this central multi-subunit enzyme is made and the role of dedicated assembly factors remains unclear. Here, we report the integrative structural analysis of a native human Pol II from the cytoplasm captured near the end of biogenesis. The complex contains Gdown1 and three biogenesis factors - RPAP2 and the critical small GTPases GPN1 and GPN3. Cryo-EM analysis of the complex reveals how Gdown1 and RPAP2 associate with Pol II and prevent the premature association of transcription factors. Further biochemical and cryo-EM analysis reveals how RPAP2 tethers GPN1-GPN3 to the complex and how the assembly of the RPAP2-GPN1-GPN3 complex is controlled by GTP hydrolysis. The combined results uncover a network of interactions that chaperone cytoplasmic Pol II to prevent aberrant interactions, reveal a molecular switch regulating biogenesis factor association, and suggest a general mechanism for the action of GPN-loop GTPase family of enzymes.

PubMed: 42443208
DOI: 10.1038/s41467-026-75416-8

Experimental method

ELECTRON MICROSCOPY (2.8 Å)