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標題: Interplay between the Poly(A) Tail, Poly(A)-Binding Protein, and Coronavirus Nucleocapsid Protein Regulates Gene Expression of Coronavirus and the Host Cell
作者: Tsai, Tsung-Lin
Lin, Ching-Houng
Lin, Chao-Nan
Lo, Chen-Yu
Wu, Hung-Yi
關鍵字: RNA synthesis;coronavirus;gene expression;nucleocapsid protein;poly(A) tail;poly(A)-binding protein;replication;translation;Animals;Cattle;Coronavirus Infections;Coronavirus, Bovine;Eukaryotic Initiation Factor-4E;Eukaryotic Initiation Factor-4G;HEK293 Cells;Humans;Nucleocapsid Proteins;Poly A;Poly(A)-Binding Proteins;Gene Expression Regulation
Project: Journal of virology, Volume 92, Issue 23
In the present study, we investigated the roles of interactions among the poly(A) tail, coronavirus nucleocapsid (N) protein, and poly(A)-binding protein (PABP) in the regulation of coronavirus gene expression. Through dissociation constant (Kd ) comparison, we found that the coronavirus N protein can bind to the poly(A) tail with high affinity, establishing N protein as a PABP. A subsequent analysis with UV cross-linking and immunoprecipitation revealed that the N protein is able to bind to the poly(A) tail in infected cells. Further examination demonstrated that poly(A) tail binding by the N protein negatively regulates translation of coronaviral RNA and host mRNA both in vitro and in cells. Although the N protein can interact with PABP and eukaryotic initiation factor 4G (eIF4G), the poor interaction efficiency between the poly(A)-bound N protein and eIF4E may explain the observed decreased translation efficiency. In addition to interaction with translation factor eIF4G, the N protein is able to interact with coronavirus nonstructural protein 9 (nsp9), a replicase protein required for replication. The study demonstrates interactions among the poly(A) tail, N protein, and PABP both in vitro and in infected cells. Of the interactions, binding of the poly(A) tail to N protein decreases the interaction efficiency between the poly(A) tail and eIF4E, leading to translation inhibition. The poly(A)-dependent translation inhibition by N protein has not been previously demonstrated and thus extends our understanding of coronavirus gene expression.IMPORTANCE Gene expression in coronavirus is a complicated and dynamic process. In this study, we demonstrated that coronavirus N protein is able to bind to the poly(A) tail with high affinity, establishing N protein as a PABP. We also show how the interplay between coronavirus 3' poly(A) tail, PABP, and N protein regulates gene expression of the coronavirus and host cell. Of the interactions, poly(A) tail binding by the N protein negatively regulates translation, and to our knowledge, this inhibition of translation by binding of the N protein to poly(A) tail has not been previously studied. Accordingly, the study provides fundamental molecular details regarding coronavirus infection and expands our knowledge of coronavirus gene expression.
DOI: 10.1128/JVI.01162-18
Appears in Collections:獸醫病理生物學所

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