title: SAMHD1 Inhibits LINE-1 Retrotransposition by Promoting Stress Granule Formation.
abstract: 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.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Hu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
authors.forename: Fengwen
authors.initials: F
authors.lastname: Xu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Mei
authors.affiliation: Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Duff
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yin
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Pang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Cen
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D003594:Cytoplasmic Granules / Q000235:genetics*; D004265:DNA Helicases; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D010766:Phosphorylation; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D034622:RNA Interference; D000067776:RNA Recognition Motif Proteins; D034741:RNA, Small Interfering; D000076106:SAM Domain and HD Domain-Containing Protein 1; D000074019:T-Cell Intracellular Antigen-1; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C113920:EIF4G1 protein, human; D039603:Eukaryotic Initiation Factor-4G; D039102:Poly(A)-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D034741:RNA, Small Interfering; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C583541:EIF2AK1 protein, human; D019892:eIF-2 Kinase; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases; D020559:Monomeric GTP-Binding Proteins