@article{179146,
  keywords = {Fluorescence Resonance Energy Transfer, Nucleic Acid Conformation, RNA, Viral, Virus Replication, Nucleotides, Orthomyxoviridae},
  author = {Nicole Robb and Aartjan Te Velthuis and Ervin Fodor and Achillefs Kapanidis},
  title = {Real-time analysis of single influenza virus replication complexes reveals large promoter-dependent differences in initiation dynamics},
  abstract = { The viral RNA (vRNA) genome of influenza viruses is replicated by the RNA-dependent RNA polymerase (RNAP) via a complementary RNA (cRNA) intermediate. The vRNA promoter can adopt multiple conformations when bound by the RNAP. However, the dynamics, determinants, and biological role of these conformations are unknown; further, little is known about cRNA promoter conformations. To probe the RNA conformations adopted during initial replication, we monitored single, surface-immobilized vRNA and cRNA initiation complexes in real-time. Our results show that, while the 3{\textquoteright} terminus of the vRNA promoter exists in dynamic equilibrium between pre-initiation and initiation conformations, the cRNA promoter exhibited very limited dynamics. Two residues in the proximal 3{\textquoteright} region of the cRNA promoter (residues absent in the vRNA promoter) allowed the cRNA template strand to reach further into the active site, limiting promoter dynamics. Our results highlight promoter-dependent differences in influenza initiation mechanisms, and advance our understanding of virus replication. },
  year = {2019},
  journal = {Nucleic Acids Res},
  volume = {47},
  pages = {6466-6477},
  month = {07/2019},
  issn = {1362-4962},
  doi = {10.1093/nar/gkz313},
  language = {eng},
}