Projects per year
Abstract / Description of output
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.
Original language | English |
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Article number | e98506 |
Number of pages | 22 |
Journal | EMBO Journal |
Volume | 37 |
Early online date | 29 Jun 2018 |
DOIs | |
Publication status | Published - 1 Aug 2018 |
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Dive into the research topics of 'RNase H2, mutated in Aicardi-Goutières syndrome, promotes LINE-1 retrotransposition'. Together they form a unique fingerprint.Projects
- 1 Finished
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MC_UU_00007/5 From Microcephaly to Genome Stability, Inflammation and Growth Regulation
1/04/18 → 31/03/23
Project: Research
Profiles
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Martin Reijns
- Deanery of Molecular, Genetic and Population Health Sciences - Senior Lecturer
- MRC Human Genetics Unit
- Edinburgh Neuroscience
Person: Academic: Research Active