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SAMHD1 Inhibits LINE-1 Retrotransposition by Promoting Stress Granule Formation
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نویسنده
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hu s. ,li j. ,xu f. ,mei s. ,le duff y. ,yin l. ,pang x. ,cen s. ,jin q. ,liang c. ,guo f.
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منبع
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plos genetics - 2015 - دوره : 11 - شماره : 7
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چکیده
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The sam domain and hd domain containing protein 1 (samhd1) inhibits retroviruses,dna viruses and long interspersed element 1 (line-1). given that in dividing cells,samhd1 loses its antiviral function yet still potently restricts line-1,we propose that,instead of blocking viral dna synthesis by virtue of its dntp triphosphohydrolase activity,samhd1 may exploit a different mechanism to control line-1. here,we report a new activity of samhd1 in promoting cellular stress granule assembly,which correlates with increased phosphorylation of eif2α and diminished eif4a/eif4g interaction. this function of samhd1 enhances sequestration of line-1 rnp in stress granules and consequent blockade to line-1 retrotransposition. in support of this new mechanism of action,depletion of stress granule marker proteins g3bp1 or tia1 abrogates stress granule formation and overcomes samhd1 inhibition of line-1. together,these data reveal a new mechanism for samhd1 to control line-1 by activating cellular stress granule pathway. © 2015 hu et al.
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آدرس
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moh key laboratory of systems biology of pathogens,institute of pathogen biology,chinese academy of medical sciences & peking union medical college,beijing, China, moh key laboratory of systems biology of pathogens,institute of pathogen biology,chinese academy of medical sciences & peking union medical college,beijing, China, moh key laboratory of systems biology of pathogens,institute of pathogen biology,chinese academy of medical sciences & peking union medical college,beijing, China, moh key laboratory of systems biology of pathogens,institute of pathogen biology,chinese academy of medical sciences & peking union medical college,beijing, China, lady davis institute,jewish general hospital,montreal,qc, Canada, moh key laboratory of systems biology of pathogens,institute of pathogen biology,chinese academy of medical sciences & peking union medical college,beijing, China, moh key laboratory of systems biology of pathogens,institute of pathogen biology,chinese academy of medical sciences & peking union medical college,beijing, China, institute of medicinal biotechnology,chinese academy of medical sciences & peking union medical college,beijing, China, moh key laboratory of systems biology of pathogens,institute of pathogen biology,chinese academy of medical sciences & peking union medical college,beijing, China, lady davis institute,jewish general hospital,montreal,qc, Canada, moh key laboratory of systems biology of pathogens,institute of pathogen biology,chinese academy of medical sciences & peking union medical college,beijing, China
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Authors
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