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Structure of Orthoreovirus RNA Chaperone SigmaNS R6A mutant
Structural highlights
FunctionSIGNS_REOVD Protein that binds to ssRNA and participates with protein mu-NS in forming the matrix of viral factories, which are large inclusions in the host cytoplasm where replication intermediates are assembled and viral RNA replication takes place (PubMed:11152519). Plays a role in the inhibition of the integrated stress response (ISR) to escape from host cell translational shutoff (PubMed:28794026). Participates in the disruption of stress granules (SG) through its association with host G3BP1 and mu-NS (PubMed:28794026).[1] [2] Publication Abstract from PubMedThe mammalian orthoreovirus (reovirus) sigmaNS protein is required for formation of replication compartments that support viral genome replication and capsid assembly. Despite its functional importance, a mechanistic understanding of sigmaNS is lacking. We conducted structural and biochemical analyses of a sigmaNS mutant that forms dimers instead of the higher-order oligomers formed by wildtype (WT) sigmaNS. The crystal structure shows that dimers interact with each other using N-terminal arms to form a helical assembly resembling WT sigmaNS filaments in complex with RNA observed using cryo-EM. The interior of the helical assembly is of appropriate diameter to bind RNA. The helical assembly is disrupted by bile acids, which bind to the same site as the N-terminal arm. This finding suggests that the N-terminal arm functions in conferring context-dependent oligomeric states of sigmaNS, which is supported by the structure of sigmaNS lacking an N-terminal arm. We further observed that sigmaNS has RNA chaperone activity likely essential for presenting mRNA to the viral polymerase for genome replication. This activity is reduced by bile acids and abolished by N-terminal arm deletion, suggesting that the activity requires formation of sigmaNS oligomers. Our studies provide structural and mechanistic insights into the function of sigmaNS in reovirus replication. Structure of orthoreovirus RNA chaperone sigmaNS, a component of viral replication factories.,Zhao B, Hu L, Kaundal S, Neetu N, Lee CH, Somoulay X, Sankaran B, Taylor GM, Dermody TS, Venkataram Prasad BV Nat Commun. 2024 Mar 19;15(1):2460. doi: 10.1038/s41467-024-46627-8. PMID:38503747[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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