SAMHD1 Inhibits LINE-1 Retrotransposition by Promoting Stress Granule Formation
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 v...
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Published in | PLoS genetics Vol. 11; no. 7; p. e1005367 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
01.07.2015
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist. Conceived and designed the experiments: FG CL QJ SH JL. Performed the experiments: SH JL FX SM YLD LY XP. Analyzed the data: FG CL QJ SC SH. Wrote the paper: FG CL SH. |
ISSN: | 1553-7404 1553-7390 1553-7404 |
DOI: | 10.1371/journal.pgen.1005367 |