%0 Journal Article
%A Benitez-Guijarro, Maria
%A Lopez-Ruiz, Cesar
%A Tarnauskaitė, Žygimantė
%A Murina, Olga
%A Mian Mohammad, Mahwish
%A Williams, Thomas C
%A Fluteau, Adeline
%A Sanchez, Laura
%A Vilar-Astasio, Raquel
%A Garcia-Canadas, Marta
%A Cano, David
%A Kempen, Marie-Jeanne Hc
%A Sanchez-Pozo, Antonio
%A Heras, Sara R
%A Jackson, Andrew P
%A Reijns, Martin Am
%A Garcia-Perez, Jose L
%T RNase H2, mutated in Aicardi-Goutières syndrome, promotes LINE-1 retrotransposition.
%D 2018
%U http://hdl.handle.net/10668/12660
%X Long INterspersed Element class 1 (LINE-1) elements are a type of abundant retrotransposons active in mammalian genomes. An average human genome contains ~100 retrotransposition-competent LINE-1s, whose activity is influenced by the combined action of cellular repressors and activators. TREX1, SAMHD1 and ADAR1 are known LINE-1 repressors and when mutated cause the autoinflammatory disorder Aicardi-Goutières syndrome (AGS). Mutations in RNase H2 are the most common cause of AGS, and its activity was proposed to similarly control LINE-1 retrotransposition. It has therefore been suggested that increased LINE-1 activity may be the cause of aberrant innate immune activation in AGS Here, we establish that, contrary to expectations, RNase H2 is required for efficient LINE-1 retrotransposition. As RNase H1 overexpression partially rescues the defect in RNase H2 null cells, we propose a model in which RNase H2 degrades the LINE-1 RNA after reverse transcription, allowing retrotransposition to be completed. This also explains how LINE-1 elements can retrotranspose efficiently without their own RNase H activity. Our findings appear to be at odds with LINE-1-derived nucleic acids driving autoinflammation in AGS.
%K Aicardi‐Goutières Syndrome
%K LINE‐1 retrotransposition
%K RNA:DNA hybrids
%K RNase H2
%~