TY - JOUR T1 - Correct and efficient initiation of viral RNA synthesis by the influenza A virus RNA polymerase JF - bioRxiv DO - 10.1101/138487 SP - 138487 AU - Judith Oymans AU - Aartjan J.W. te Velthuis Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/05/16/138487.abstract N2 - The influenza A virus uses an RNA-dependent RNA polymerase (RdRp) to replicate and transcribe its genome. To ensure that the genome is copied correctly, the RdRp has been proposed to realign the initiation product of viral RNA (vRNA) synthesis from the internal initiation site to the 3’ end of the complementary RNA (cRNA) template before extending the nascent vRNA. Here we show that this process is essential for viral RNA synthesis and that the RdRp uses a mechanism involving the priming loop to enforce realignment during replication. We also find that realignment plays a role in viral mRNA synthesis, enabling the RdRp to handle sequence variation among the primers that it snatches from host mRNAs to prime viral mRNA synthesis. Overall, these observations advance our mechanistic understanding of how the influenza A virus initiates replication and transcription correctly and efficiently. ER -