title: Modulation of LINE-1 and Alu/SVA retrotransposition by Aicardi-Goutières syndrome-related SAMHD1.
abstract: Long interspersed elements 1 (LINE-1) occupy at least 17% of the human genome and are its only active autonomous retrotransposons. However, the host factors that regulate LINE-1 retrotransposition are not fully understood. Here, we demonstrate that the Aicardi-Goutières syndrome gene product SAMHD1, recently revealed to be an inhibitor of HIV/simian immunodeficiency virus (SIV) infectivity and neutralized by the viral Vpx protein, is also a potent regulator of LINE-1 and LINE-1-mediated Alu/SVA retrotransposition. We also found that mutant SAMHD1s of Aicardi-Goutières syndrome patients are defective in LINE-1 inhibition. Several domains of SAMHD1 are critical for LINE-1 regulation. SAMHD1 inhibits LINE-1 retrotransposition in dividing cells. An enzymatic active site mutant SAMHD1 maintained substantial anti-LINE-1 activity. SAMHD1 inhibits ORF2p-mediated LINE-1 reverse transcription in isolated LINE-1 ribonucleoproteins by reducing ORF2p level. Thus, SAMHD1 may be a cellular regulator of LINE-1 activity that is conserved in mammals.
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, 519 E. Minzhu Avenue, Changchun, Jilin Province 130061, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhao
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: John L
authors.initials: JL
authors.lastname: Goodier
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Sean L
authors.initials: SL
authors.lastname: Evans
authors.forename: Linzhang
authors.initials: L
authors.lastname: Li
authors.forename: Wenyan
authors.initials: W
authors.lastname: Zhang
authors.forename: Ling E
authors.initials: LE
authors.lastname: Cheung
authors.forename: Guanjun
authors.initials: G
authors.lastname: Wang
authors.forename: Haig H
authors.initials: HH
authors.lastname: Kazazian
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
mesh_terms: D020087:Alu Elements; D020274:Autoimmune Diseases of the Nervous System / Q000235:genetics*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D009421:Nervous System Malformations / Q000235:genetics*; D016366:Open Reading Frames; D012261:Ribonucleoproteins / Q000235:genetics; D000076106:SAM Domain and HD Domain-Containing Protein 1; D016415:Sequence Alignment; D014162:Transfection
chemical_list: D012261:Ribonucleoproteins; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins
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