Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1

Ke Zhao, Juan Du, Xue Han, John L. Goodier, Peng Li, Xiaohong Zhou, Wei Wei, Sean L. Evans, Linzhang Li, Wenyan Zhang, Ling E. Cheung, Guanjun Wang, Haig H. Kazazian, Xiao Fang Yu

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)1108-1115
Number of pages8
JournalCell Reports
Volume4
Issue number6
DOIs
StatePublished - Sep 26 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Zhao, K., Du, J., Han, X., Goodier, J. L., Li, P., Zhou, X., Wei, W., Evans, S. L., Li, L., Zhang, W., Cheung, L. E., Wang, G., Kazazian, H. H., & Yu, X. F. (2013). Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1. Cell Reports, 4(6), 1108-1115. https://doi.org/10.1016/j.celrep.2013.08.019