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A mechanism for the activation of the influenza virus transcriptase

DOI: 10.1016/j.molcel.2018.05.011 DOI Help

Authors: Itziar Serna Martin (University of Oxford) , Narin Hengrung (University of Oxford) , Max Renner (University of Oxford) , Jane Sharps (University of Oxford) , Mónica Martínez-alonso (University of Oxford) , Simonas Masiulis (University of Oxford) , Jonathan M. Grimes (University of Oxford) , Ervin Fodor (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell

State: Published (Approved)
Published: June 2018
Diamond Proposal Number(s): 8423

Open Access Open Access

Abstract: 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 (FluPolC) 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 by FluPolC are enhanced in the presence of pS5-CTD. Mutations of amino acids in the CTD-binding site reduce viral mRNA synthesis. We propose a model for the activation of the influenza virus transcriptase through its association with pS5-CTD of Pol II.

Journal Keywords: influenza virus; RNA polymerase; transcriptase; cap snatching; transcription; replication; Pol II; CTD

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

Documents:
1-s2.0-S1097276518303617-main.pdf

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