RNase H2, mutated in Aicardi-Goutières syndrome, promotes LINE-1 retrotransposition Benitez Guijarro, María Sánchez Pozo, Antonio Rodríguez Heras, Sara Aicardi-Goutières Syndrome LINE-1 retrotransposition RNA:DNA hybrids 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. 2019-11-25T10:11:08Z 2019-11-25T10:11:08Z 2018-06-29 info:eu-repo/semantics/article Benitez‐Guijarro, M., Lopez‐Ruiz, C., Tarnauskaitė, Ž., Murina, O., Mohammad, M. M., Williams, T. C., ... & Cano, D. (2018). RNase H2, mutated in Aicardi‐Goutières syndrome, promotes LINE‐1 retrotransposition. The EMBO journal, 37(15). http://hdl.handle.net/10481/58045 10.15252/embj.201798506 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España EMBO Press