8Z8N

Cryo-EM structure of Thogoto virus polymerase in transcription pre-initiation conformation 3

Summary for 8Z8N

• Entry DOI: 10.2210/pdb8z8n/pdb
• EMDB information: 39849
• Descriptor: Polymerase acidic protein, RNA-directed RNA polymerase catalytic subunit, Polymerase basic protein 2, ... (5 entities in total)
• Functional Keywords: rna polymerase, transcription
• Biological source: Thogoto virus (isolate SiAr 126) (Tho); More
• Total number of polymer chains: 5
• Total formula weight: 258653.39

Authors

Xue, L.,Chang, T.,Li, Z.,Zhao, H.,Li, M.,He, J.,Chen, X.,Xiong, X. (deposition date: 2024-04-22, release date: 2024-05-29, Last modification date: 2024-06-19)

Primary citation

Xue, L.,Chang, T.,Li, Z.,Wang, C.,Zhao, H.,Li, M.,Tang, P.,Wen, X.,Yu, M.,Wu, J.,Bao, X.,Wang, X.,Gong, P.,He, J.,Chen, X.,Xiong, X.
Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses.
Nat Commun, 15:4620-4620, 2024

PubMed Abstract: Influenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV transcribes mRNA without the extraneous 5' end sequences derived from cap-snatching in influenza virus mRNA. Here, we report cryo-EM structures to characterize THOV polymerase RNA synthesis initiation and elongation. The structures demonstrate that THOV RNA transcription and replication are able to start with short dinucleotide primers and that the polymerase cap-snatching machinery is likely non-functional. Triggered by RNA synthesis, asymmetric THOV polymerase dimers can form without the involvement of host factors. We confirm that, distinctive from influenza viruses, THOV-polymerase RNA synthesis is weakly dependent of the host factors ANP32A/B/E in human cells. This study demonstrates varied mechanisms in RNA synthesis and host factor utilization among orthomyxoviruses, providing insights into the mechanisms behind thogotoviruses' broad-infectivity range.

PubMed: 38816392
DOI: 10.1038/s41467-024-48848-3

Experimental method

ELECTRON MICROSCOPY (2.79 Å)