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Cytoplasmic Viral RNA-Dependent RNA Polymerase Disrupts the Intracellular Splicing Machinery by Entering the Nucleus and Interfering with Prp8
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نویسنده
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liu y.-c. ,kuo r.-l. ,lin j.-y. ,huang p.-n. ,huang y. ,liu h. ,arnold j.j. ,chen s.-j. ,wang r.y.-l. ,cameron c.e. ,shih s.-r.
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منبع
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plos pathogens - 2014 - دوره : 10 - شماره : 6
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چکیده
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The primary role of cytoplasmic viral rna-dependent rna polymerase (rdrp) is viral genome replication in the cellular cytoplasm. however,picornaviral rdrp denoted 3d polymerase (3dpol) also enters the host nucleus,where its function remains unclear. in this study,we describe a novel mechanism of viral attack in which 3dpol enters the nucleus through the nuclear localization signal (nls) and targets the pre-mrna processing factor 8 (prp8) to block pre-mrna splicing and mrna synthesis. the fingers domain of 3dpol associates with the c-terminal region of prp8,which contains the jab1/mpn domain,and interferes in the second catalytic step,resulting in the accumulation of the lariat form of the splicing intermediate. endogenous pre-mrnas trapped by the prp8-3dpol complex in enterovirus-infected cells were identified and classed into groups associated with cell growth,proliferation,and differentiation. our results suggest that picornaviral rdrp disrupts pre-mrna splicing processes,that differs from viral protease shutting off cellular transcription and translation which contributes to the pathogenesis of viral infection. © 2014 liu et al.
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آدرس
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research center for emerging viral infections,college of medicine,chang gung university,tao-yuan,taiwan,graduate institute of biomedical sciences,college of medicine,chang gung university,tao-yuan, Taiwan, research center for emerging viral infections,college of medicine,chang gung university,tao-yuan,taiwan,graduate institute of biomedical sciences,college of medicine,chang gung university,tao-yuan,taiwan,department of medical biotechnology and laboratory science,college of medicine,chang gung university,tao-yuan, Taiwan, school of medical laboratory science and biotechnology,taipei medical university,taipei, Taiwan, research center for emerging viral infections,college of medicine,chang gung university,tao-yuan, Taiwan, molecular medicine research center,chang gung university,tao-yuan, Taiwan, molecular medicine research center,chang gung university,tao-yuan, Taiwan, department of biochemistry and molecular biology,pennsylvania state university,university park,pa, United States, molecular medicine research center,chang gung university,tao-yuan, Taiwan, research center for emerging viral infections,college of medicine,chang gung university,tao-yuan,taiwan,department of biomedical sciences and graduate institutes of biomedical sciences,college of medicine,chang gung university,tao-yuan, Taiwan, department of biochemistry and molecular biology,pennsylvania state university,university park,pa, United States, research center for emerging viral infections,college of medicine,chang gung university,tao-yuan,taiwan,graduate institute of biomedical sciences,college of medicine,chang gung university,tao-yuan,taiwan,department of medical biotechnology and laboratory science,college of medicine,chang gung university,tao-yuan,taiwan,clinical virology laboratory,chang gung memorial hospital,tao-yuan, Taiwan
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Authors
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