Back to Search
Start Over
RNase H2, mutated in Aicardi-Goutières syndrome, promotes LINE-1 retrotransposition.
- Source :
-
The EMBO journal [EMBO J] 2018 Aug 01; Vol. 37 (15). Date of Electronic Publication: 2018 Jun 29. - Publication Year :
- 2018
-
Abstract
- 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.<br /> (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)
- Subjects :
- Cell Line, Tumor
Gene Knockout Techniques
HCT116 Cells
HeLa Cells
Humans
Reverse Transcription genetics
Ribonuclease H biosynthesis
Autoimmune Diseases of the Nervous System genetics
Long Interspersed Nucleotide Elements genetics
Nervous System Malformations genetics
Ribonuclease H genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2075
- Volume :
- 37
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 29959219
- Full Text :
- https://doi.org/10.15252/embj.201798506