1. Modulation of LINE-1 and Alu/SVA retrotransposition by Aicardi-Goutières syndrome-related SAMHD1.
- Author
-
Zhao K, Du J, Han X, Goodier JL, Li P, Zhou X, Wei W, Evans SL, Li L, Zhang W, Cheung LE, Wang G, Kazazian HH Jr, and Yu XF
- Subjects
- Alu Elements, HEK293 Cells, HeLa Cells, Humans, Open Reading Frames, Ribonucleoproteins genetics, SAM Domain and HD Domain-Containing Protein 1, Sequence Alignment, Transfection, Autoimmune Diseases of the Nervous System genetics, Long Interspersed Nucleotide Elements, Monomeric GTP-Binding Proteins genetics, Nervous System Malformations genetics
- 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., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF