A Coronaviral Pore-Replicase Complex Drives RNA Synthesis in Double Membrane Vesicles
Chen, A.; Lupan, A.-M.; Quek, R. T.; Stanciu, S. G.; Asaftei, M.; Stanciu, G. A.; Hardy, K.; Magalhaes, T.; Silver, P. A.; Mitchison, T.; Salic, A.
Show abstract
Coronavirus-infected cells contain double-membrane vesicles (DMVs) that are key for viral RNA replication and transcription, perforated by hexameric pores connecting the vesicular lumen to the cytoplasm. How pores form and traverse two membranes, and how DMVs organize RNA synthesis, is unknown. Using structure prediction and functional assays, we show that the non-structural viral membrane protein nsp4 is the key DMV pore organizer, spanning the double membrane and forming most of the pore lining. Nsp4 interacts with nsp3 on the cytoplasmic side and with the viral replicase inside the DMV. Newly synthesized mRNAs exit the DMV into the cytoplasm, passing through a narrow ring of conserved nsp4 residues. Steric constraints imposed by the ring predict that modified nucleobases block mRNA transit, with broad spectrum anti-coronaviral activity.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- QTQTN motif upstream of the furin-cleavage site plays key role in SARS-CoV-2 infection and pathogenesis. 96%
- A Molecular Mechanism for Probabilistic Bet-hedging and its Role in Viral Latency 96%
- Nodavirus RNA Replication Crown Architecture Reveals Proto-Crown Precursor and Viral Protein A Conformational Switching 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.