8pnp | pdb_00008pnp
Influenza A/H7N9 polymerase in pre-initiation state with continuous Pol II pS5 CTD peptide mimic bound in site 1A/2A
Structural highlights
FunctionM9TI86_9INFA Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.[HAMAP-Rule:MF_04063][SAAS:SAAS00956500] Publication Abstract from PubMedThe current model is that the influenza virus polymerase (FluPol) binds either to host RNA polymerase II (RNAP II) or to the acidic nuclear phosphoprotein 32 (ANP32), which drives its conformation and activity towards transcription or replication of the viral genome, respectively. Here, we provide evidence that the FluPol-RNAP II binding interface, beyond its well-acknowledged function in cap-snatching during transcription initiation, has also a pivotal role in replication of the viral genome. Using a combination of cell-based and in vitro approaches, we show that the RNAP II C-terminal-domain, jointly with ANP32, enhances FluPol replication activity. We observe successive conformational changes to switch from a transcriptase to a replicase conformation in the presence of the bound RNPAII C-terminal domain and propose a model in which the host RNAP II is the anchor for transcription and replication of the viral genome. Our data open new perspectives on the spatial coupling of viral transcription and replication and the coordinated balance between these two activities. The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome.,Krischuns T, Arragain B, Isel C, Paisant S, Budt M, Wolff T, Cusack S, Naffakh N Nat Commun. 2024 Feb 5;15(1):1064. doi: 10.1038/s41467-024-45205-2. PMID:38316757[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
