RNase H2, mutated in Aicardi-Goutieres syndrome, promotes LINE-1 retrotransposition
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.
Source: EMBO Journal - Category: Molecular Biology Authors: Benitez-Guijarro, M., Lopez-Ruiz, C., Tarnauskaite, Z., Murina, O., Mian Mohammad, M., Williams, T. C., Fluteau, A., Sanchez, L., Vilar-Astasio, R., Garcia-Canadas, M., Cano, D., Kempen, M.-J. H., Sanchez-Pozo, A., Heras, S. R., Jackson, A. P., Reijns, M. Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Immunology, Molecular Biology of Disease Articles Source Type: research