biostudies-literatureSerna Martin IMedical Research CouncilSeventh Framework ProgrammeWellcome Trust1101-1110.e4https://www.ebi.ac.uk/biostudies/studies/S-EPMC6024077biostudies-literatureUnknown70(6)Influenza virus RNA polymerase (FluPol), a heterotrimer composed of PB1, PB2, and PA subunits (P3 in influenza C), performs both transcription and replication of the viral RNA genome. For transcription, FluPol interacts with the C-terminal domain (CTD) of RNA polymerase II (Pol II), which enables FluPol to snatch capped RNA primers from nascent host RNAs. Here, we describe the co-crystal structure of influenza C virus polymerase (FluPol_C) bound to a Ser5-phosphorylated CTD (pS₅-CTD) peptide. The position of the CTD-binding site at the interface of PB1, P3, and the flexible PB2 C-terminal domains suggests that CTD binding stabilizes the transcription-competent conformation of FluPol. In agreement, both cap snatching and capped primer-dependent transcription initiation Molecular cellA Mechanism for the Activation of the Influenza Virus Transcriptase.PMC6024077203141/Z/16/ZMR/R009945/11374922084655/Z/08/Z200835/Z/16/Z092931/Z/10/Z204703/Z/16/ZPIEF-GA-2012-328746MR/K000241/1Fodor EMartinez-Alonso MRenner MGrimes JMHengrung NSharps JMasiulis SSerna Martin IfalseA Mechanism for the Activation of the Influenza Virus Transcriptase.Influenza virus RNA polymerase (FluPol), a heterotrimer composed of PB1, PB2, and PA subunits (P3 in influenza C), performs both transcription and replication of the viral RNA genome. For transcription, FluPol interacts with the C-terminal domain (CTD) of RNA polymerase II (Pol II), which enables FluPol to snatch capped RNA primers from nascent host RNAs. Here, we describe the co-crystal structure of influenza C virus polymerase (FluPol_C) bound to a Ser5-phosphorylated CTD (pS₅-CTD) peptide. The position of the CTD-binding site at the interface of PB1, P3, and the flexible PB2 C-terminal domains suggests that CTD binding stabilizes the transcription-competent conformation of FluPol. In agreement, both cap snatching and capped primer-dependent transcription initiation 2018-01-01T00:00:00Z2018 Jun2026-04-30T21:44:08.353Z2019-03-26T23:44:43ZS-EPMC60240772991011210.1016/j.molcel.2018.05.011