The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA.
Zinc-finger antiviral protein (ZAP) is a host antiviral factor that specifically inhibits the replication of Moloney murine leukemia virus (MLV) and Sindbis virus (SIN) by preventing accumulation of the viral mRNA in the cytoplasm. In previous studies, we demonstrated that ZAP directly binds to its specific target mRNAs. In this article, we provide evidence indicating that ZAP recruits the RNA processing exosome to degrade the target RNA. ZAP comigrated with the exosome in sucrose or glycerol velocity gradient centrifugation. Immunoprecipitation of ZAP coprecipitated the exosome components. In vitro pull-down assays indicated that ZAP directly interacted with the exosome component hRrp46p and that the binding region of ZAP was mapped to amino acids 224-254. Depletion of the exosome component hRrp41p or hRrp46p with small interfering RNA significantly reduced ZAP's destabilizing activity. These findings suggest that ZAP is a trans-acting factor that modulates mRNA stability.
Guo
Xuemin
X
Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Ma
Jing
J
Sun
Jing
J
Gao
Guangxia
G
D000951:Antigens, Neoplasm / Q000502:physiology; D000954:Antigens, Surface / Q000502:physiology; D001665:Binding Sites; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005095:Exoribonucleases / Q000502:physiology; D063326:Exosome Multienzyme Ribonuclease Complex; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins; D016335:Zinc Fingers
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D002352:Carrier Proteins; C467564:EXOSC5 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C465959:Zc3hav1 protein, rat; C415835:EXOSC4 protein, human; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex