Nature Communications, 4 November, 2025, DOI：https://doi.org/10.1038/s41467-025-64741-z

Coupling of polymerase-nucleoprotein-RNA in an influenza virus mini ribonucleoprotein complex

Huiling Kang, Yunxiang Yang, Yixiao Liu, Mingyu Li, Lejin Zhang, Yuqi Lin, Leander Witte, Kuang-Yu Chen, Wenya Song, Zhili Xu, Xiaojing He, Luke W. Guddat, Yu Guo, Liming Yan, Yan Gao, Ervin Fodor, Zihe Rao & Zhiyong Lou

Abstract

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.

文章链接：https://www.nature.com/articles/s41467-025-64741-z