RNase H2, mutated in Aicardi‐Goutières syndrome, promotes LINE‐1 retrotransposition

• DOI: 10.15252/embj.201798506
• Publication Date: 2018-06-29T07:55:15Z
• Authors: Maria Benitez‐Gui...; Cesar Lopez‐Ruiz; Žygimantė Tarnaus...; Olga Murina; Mahwish Mian Moha...; Thomas C Williams; Adeline Fluteau; Laura Sanchez; Raquel Vilar‐Astasio; Marta Garcia‐Canadas; David Cano; Marie‐Jeanne HC K...; Antonio Sanchez‐Pozo; Sara R Heras; Andrew P Jackson; Martin AM Reijns; Jose L Garcia‐Perez
• Keywords: Retrotransposon; RNase H

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 cellular repressors and activators. TREX1, SAMHD1 ADAR1 known LINE-1 when mutated cause autoinflammatory disorder Aicardi-Goutières syndrome (AGS). Mutations RNase H2 most common AGS, its was proposed to similarly control retrotransposition. It has therefore been suggested that increased may be aberrant innate immune activation AGS Here, we establish that, contrary expectations, required for efficient As H1 overexpression partially rescues defect null cells, propose model which degrades RNA after reverse transcription, allowing retrotransposition completed. This also explains how can retrotranspose efficiently without their own H activity. Our findings appear at odds with LINE-1-derived nucleic acids driving autoinflammation AGS.