@article{bd759ab1e9224ee3ac56a2bd5e4c0558,
title = "Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Gouti{\`e}res 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-Gouti{\`e}res 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-Gouti{\`e}res 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",
author = "Ke Zhao and Juan Du and Xue Han and Goodier, {John L.} and Peng Li and Xiaohong Zhou and Wei Wei and Evans, {Sean L.} and Linzhang Li and Wenyan Zhang and Cheung, {Ling E.} and Guanjun Wang and Kazazian, {Haig H.} and Yu, {Xiao Fang}",
note = "Funding Information: We thank Drs. J. Boeke, D. Hancks, T. Inoue, M. Stevenson, and R. Siliciano for critical reagents; Y. Rui, W. Zheng, H. Guo, and J. Hou for technical assistance; R. Markham, J. Margolick, and J. Bream for thoughtful discussions; and D. McClellan for editorial assistance. We also wish to thank staff within the Mass Spectrometry Core and the Institute for Basic Biomedical Sciences Microscope Facility at Johns Hopkins School of Medicine for their technical assistance. The following reagent was obtained through the AIDS Research and Reference Reagents Program, Division of AIDS, NIAID, NIH: pHEF-VSVG (L.-J. Chang). This work was supported in part by funding from the Chinese Ministry of Science and Technology (2012CB911100 and No. 2013ZX0001-005) and Chinese Ministry of Education (IRT1016), the Key Laboratory of Molecular Virology, Jilin Province (20102209), China, a grant (2R56AI62644-6) from the NIAID, and a grant (1RC4MH092880-01) from the NIMH to H.H.K. K.Z., J.D., X.Z., J.L.G., P.L., W.W., S.L.E., X.H., L.L., and L.E.C. performed experiments. K.Z., J.D., J.L.G., L.E.C., W.Z., G.W., H.H.K., and X.-F.Y. analyzed the data. K.Z. and X.-F.Y. wrote the paper with help from all authors. X.-F.Y. directed the project. ",
year = "2013",
month = sep,
day = "26",
doi = "10.1016/j.celrep.2013.08.019",
language = "English (US)",
volume = "4",
pages = "1108--1115",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}