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Publication Abstract from PubMed

The 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.