Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2013-09, Vol.4 (6), p.1108-1115

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •SAMHD1 is as a potent inhibitor of non-LTR retrotransposons in dividing cells•AGS-related SAMHD1 mutants have poor activity against LINE-1 retrotransposition•SAMHD1 suppresses HIV-1 and LINE-1 through distinct mechanisms•SAMHD1 inhibits ORF2p-mediated LINE-1 reverse transcription by reducing ORF2 level Long interspersed elements 1 (LINE-1) are active autonomous retrotransposons that occupy 17% of the human genome. The host factors that regulate LINE-1 retrotransposition are not fully understood. In this study, Yu and colleagues show that the Aicardi-Goutières syndrome (AGS) gene product, SAMHD1, is a potent regulator of LINE-1 retrotransposition. SAMHD1 mutants linked to AGS are defective in LINE-1 inhibition. Although SAMHD1 has also recently been shown to suppress HIV-1, the authors find that suppression of LINE-1 occurs through a distinct mechanism.