Coupling of polymerase-nucleoprotein-RNA in an influenza virus mini ribonucleoprotein complex
Influenza virus ribonucleoprotein complexes (RNPs), composed of the polymerase complex (FluPol), nucleoprotein (NP), and RNA, are essential for replication and transcription. We report atomic-resolution cryo-EM structures of mini-vRNPs in two states: FluPol located inside (State-In) or at the outer rim (State-Out) of the NP-RNA ring. In both states, the 5' and 3' termini of vRNA are bound to FluPol as previously reported. One NP (NP-0) contacts PA/PB1 of FluPol and binds the distal double-stranded vRNA promoter, with its D72-K90 loop inserting into the RNA fork; separated strands occupy NP-0 RNA-binding grooves. Grooves from other NPs form a continuous RNA-protective path, consistent with negative-strand RNA virus mechanisms. In State-In, interfaces for FluPol dimerization or Pol II interaction are blocked, but fully exposed in State-Out. These structures reveal detailed FluPol-NP-RNA coupling and suggest a conformational shift in RNPs during the viral life cycle.
Authors
- Yan Gao (ORCID: https://orcid.org/0000-0002-0364-6427)
- Xiaojing He (ORCID: https://orcid.org/0000-0003-3917-1133)
- Leander Witte (ORCID: https://orcid.org/0000-0002-4704-8461)
- Huiling Kang (ORCID: https://orcid.org/0000-0002-7610-0281)
- Yu Guo (ORCID: https://orcid.org/0000-0002-8109-7515)
- Kuang‐Yu Chen (ORCID: https://orcid.org/0000-0001-7581-6766)
- Liming Yan (ORCID: https://orcid.org/0000-0003-0648-9604)
- Ervin Fodor (ORCID: https://orcid.org/0000-0003-3249-196X)
- Zihe Rao (ORCID: https://orcid.org/0000-0001-9866-2384)
- Zhiyong Lou (ORCID: https://orcid.org/0000-0003-2728-881X)
- Luke W. Guddat (ORCID: https://orcid.org/0000-0002-8204-8408)
- Mingyu Li (ORCID: https://orcid.org/0000-0001-6251-649X)
- Yuqi Lin (ORCID: https://orcid.org/0000-0002-3019-5684)
- Yunxiang Yang
- Yixiao Liu (ORCID: https://orcid.org/0000-0001-6973-2515)
- L. M. Zhang (ORCID: https://orcid.org/0000-0003-2570-0663)
- Zhili Xu
- Wenya Song
Institutions
- Hebei Medical University (CN)
- University of Science and Technology of China (CN)
- The University of Queensland (AU)
- Capital Medical University (CN)
- Chinese Academy of Sciences (CN)
- Nankai University (CN)
- ShanghaiTech University (CN)
- University of Oxford (GB)
- Fourth Hospital of Hebei Medical University (CN)
- Wuhan Institute of Virology (CN)
- Institute of Biophysics (CN)
- Guangzhou Automobile Group (China) (CN)
- State Key Laboratory of Medicinal Chemical Biology
- State Key Laboratory of Virology
- Huazhong University of Science and Technology (CN)
- Tsinghua University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-04
- DOI
- https://doi.org/10.1038/s41467-025-64741-z
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Tsinghua University
- Medical Research Council