@article{22333,
  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.},
  author       = {Hlavata, Annamaria and Neuditschko, Benjamin and Schellhaas, Ulla and Plaschka, Clemens and Herzog, Franz and Bernecky, Carrie A},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Structure of cytoplasmic RNA polymerase II}},
  doi          = {10.1038/s41467-026-75416-8},
  year         = {2026},
}