---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '22333'
abstract:
- lang: eng
  text: 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.
acknowledged_ssus:
- _id: LifeSc
- _id: EM-Fac
- _id: ScienComp
- _id: PreCl
acknowledgement: We thank A. Salmazo for assistance with Pol II purification. We thank
  staff at the Vienna BioCenter Core Facilities (VBCF) Proteomics facility for immunoprecipitation-mass
  spectrometry analysis, and J.A. Stopp for assistance with IP-MS data visualization.
  This research was further supported by the Scientific Service Units (SSUs) of ISTA
  through resources provided by the Lab Support Facility (LSF), Electron Microscopy
  Facility (EMF), Scientific Computing (SciComp), and the Preclinical Facility (PCF).
  F.H. was funded by the Endowed Professorship of the Lower Austria Research Funding
  Agency (GFF NÖ) and by the Austrian Research Promotion Agency (FFG) through the
  COIN Establishment Grant n.o. 45624401.
article_processing_charge: Yes
article_type: original
author:
- first_name: Annamaria
  full_name: Hlavata, Annamaria
  id: 36062FEC-F248-11E8-B48F-1D18A9856A87
  last_name: Hlavata
- first_name: Benjamin
  full_name: Neuditschko, Benjamin
  last_name: Neuditschko
- first_name: Ulla
  full_name: Schellhaas, Ulla
  last_name: Schellhaas
- first_name: Clemens
  full_name: Plaschka, Clemens
  last_name: Plaschka
- first_name: Franz
  full_name: Herzog, Franz
  last_name: Herzog
- first_name: Carrie A
  full_name: Bernecky, Carrie A
  id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
  last_name: Bernecky
  orcid: 0000-0003-0893-7036
biorxivid: 1
citation:
  ama: Hlavata A, Neuditschko B, Schellhaas U, Plaschka C, Herzog F, Bernecky C. Structure
    of cytoplasmic RNA polymerase II. <i>Nature Communications</i>. 2026. doi:<a href="https://doi.org/10.1038/s41467-026-75416-8">10.1038/s41467-026-75416-8</a>
  apa: Hlavata, A., Neuditschko, B., Schellhaas, U., Plaschka, C., Herzog, F., &#38;
    Bernecky, C. (2026). Structure of cytoplasmic RNA polymerase II. <i>Nature Communications</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41467-026-75416-8">https://doi.org/10.1038/s41467-026-75416-8</a>
  chicago: Hlavata, Annamaria, Benjamin Neuditschko, Ulla Schellhaas, Clemens Plaschka,
    Franz Herzog, and Carrie Bernecky. “Structure of Cytoplasmic RNA Polymerase II.”
    <i>Nature Communications</i>. Springer Nature, 2026. <a href="https://doi.org/10.1038/s41467-026-75416-8">https://doi.org/10.1038/s41467-026-75416-8</a>.
  ieee: A. Hlavata, B. Neuditschko, U. Schellhaas, C. Plaschka, F. Herzog, and C.
    Bernecky, “Structure of cytoplasmic RNA polymerase II,” <i>Nature Communications</i>.
    Springer Nature, 2026.
  ista: Hlavata A, Neuditschko B, Schellhaas U, Plaschka C, Herzog F, Bernecky C.
    2026. Structure of cytoplasmic RNA polymerase II. Nature Communications.
  mla: Hlavata, Annamaria, et al. “Structure of Cytoplasmic RNA Polymerase II.” <i>Nature
    Communications</i>, Springer Nature, 2026, doi:<a href="https://doi.org/10.1038/s41467-026-75416-8">10.1038/s41467-026-75416-8</a>.
  short: A. Hlavata, B. Neuditschko, U. Schellhaas, C. Plaschka, F. Herzog, C. Bernecky,
    Nature Communications (2026).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: "The\r\nc ryo EM maps generated in this study were deposited
  to the EM Data Bank under the\r\naccession codes: EMD 55583 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
  55583\r\n(Pol II Gdown1 RPAP2 composite map), EMD 55578\r\n[https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
  55578 Pol II Gdown1 RPAP2 Pol II core\r\nmap EMD 55579 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
  55579 Pol II\r\nGdown1 RPAP2 Pol II stalk map EMD 55580\r\n[https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
  55580 Pol II Gdown1 RPAP2 RPAP2\r\nmap EMD 55581 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
  55 581 Pol II\r\nGdown1 RPAP2 Gdown1 N terminus map EMD 55582\r\n[https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
  55582 Pol II Gdown1 RPAP2 Gdown1\r\nC terminus map and EMD 55585 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD\r\n55585
  RPAP2 GPN1 GPN3 map Model coordi nates were deposited to the PDBe under\r\nthe accession
  codes: 9T5H [http://doi.org/10.2210/pdb 9T5H / (Pol II Gdown1\r\nRPAP2 complex structure)
  and 9T5J [http://doi.org/10.2210/pdb 9T5H / (GPN1\r\nGPN3 RPAP2 structure). Immunoprecipitation
  mass spectrometry and crosslinking mass\r\nspectrometry proteomics data have been
  deposited to the ProteomeXchange Consortium\r\nvia the PRIDE partner repository
  with the dataset identifiers PXD071638\r\n[http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD
  071638 and\r\nP XD070852\r\n[http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD
  070852\r\nAlphaFold3 structure predictions have been deposited to the Zenodo repository\r\nhttps://doi.org/10.5281/zenodo.20687910
  P reviously published model coordinates\r\nwere utilized and are available at the
  PDB under the accession codes 8QEP\r\n[http://doi.org/10.2210/pdb 8QEP / 9BZ 0 [http://doi.org/10.2210/pdb
  9BZ 0 /\r\nand 7B7U [http://doi.org/10.2210/pdb 7B7U / Source Data are provided
  with this\r\npaper."
date_created: 2026-07-14T07:27:59Z
date_published: 2026-07-13T00:00:00Z
date_updated: 2026-07-16T11:29:31Z
day: '13'
ddc:
- '570'
department:
- _id: CaBe
doi: 10.1038/s41467-026-75416-8
external_id:
  biorxivid:
  - 10.64898/2025.12.10.692585
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41467-026-75416-8
month: '07'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Structure of cytoplasmic RNA polymerase II
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...