SAMHD1 Inhibits LINE-1 Retrotransposition by Promoting Stress Granule Formation: e1005367

• Published in: PLoS genetics 2015-07, Vol.11 (7)
• Main Authors: Hu, Siqi, Li, Jian, Xu, Fengwen, Mei, Shan, Duff, Yann Le, Yin, Lijuan, Pang, Xiaojing, Cen, Shan, Jin, Qi, Liang, Chen, Guo, Fei
• Format: Article
• Language: English
• Subjects: Cell growth; Deoxyribonucleic acid; DNA; Experiments; Genetic testing; Genomes; Herpes viruses; HIV; Human immunodeficiency virus; Kinases; Lymphocytes; Medical research; Phosphorylation; Proteins; Retrovirus
• ISSN: 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1005367

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 eIF2[alpha] 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.