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RNase H2, mutated in Aicardi‐Goutières syndrome, promotes LINE‐1 retrotransposition
Author(s) -
BenitezGuijarro Maria,
LopezRuiz Cesar,
Tarnauskaitė Žygimantė,
Murina Olga,
Mian Mohammad Mahwish,
Williams Thomas C,
Fluteau Adeline,
Sanchez Laura,
VilarAstasio Raquel,
GarciaCanadas Marta,
Cano David,
Kempen MarieJeanne HC,
SanchezPozo Antonio,
Heras Sara R,
Jackson Andrew P,
Reijns Martin AM,
GarciaPerez Jose L
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798506
Subject(s) - general hospital , molecular genetics , medical genetics , library science , genetics , medicine , biology , family medicine , gene , computer science
Long IN terspersed 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. TREX 1, SAMHD 1 and ADAR 1 are known LINE ‐1 repressors and when mutated cause the autoinflammatory disorder Aicardi‐Goutières syndrome ( AGS ). Mutations in RN ase 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, RN ase H2 is required for efficient LINE ‐1 retrotransposition. As RNase H1 overexpression partially rescues the defect in RN ase H2 null cells, we propose a model in which RN ase 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 RN ase H activity. Our findings appear to be at odds with LINE ‐1‐derived nucleic acids driving autoinflammation in AGS .