Journal
CELL REPORTS
Volume 4, Issue 6, Pages 1108-1115Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2013.08.019
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Funding
- Chinese Ministry of Science and Technology [2012CB911100, 2013ZX0001-005]
- Chinese Ministry of Education [IRT1016]
- Key Laboratory of Molecular Virology, Jilin Province, China [20102209]
- NIAID [2R56AI62644-6]
- NIMH [1RC4MH092880-01]
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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-Goutieres 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-Goutieres 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.
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