RT Journal Article
T1 RNase H2, mutated in Aicardi-Goutières syndrome, promotes LINE-1 retrotransposition.
A1 Benitez-Guijarro, Maria
A1 Lopez-Ruiz, Cesar
A1 Tarnauskaitė, Žygimantė
A1 Murina, Olga
A1 Mian Mohammad, Mahwish
A1 Williams, Thomas C
A1 Fluteau, Adeline
A1 Sanchez, Laura
A1 Vilar-Astasio, Raquel
A1 Garcia-Canadas, Marta
A1 Cano, David
A1 Kempen, Marie-Jeanne Hc
A1 Sanchez-Pozo, Antonio
A1 Heras, Sara R
A1 Jackson, Andrew P
A1 Reijns, Martin Am
A1 Garcia-Perez, Jose L
K1 Aicardi‐Goutières Syndrome
K1 LINE‐1 retrotransposition
K1 RNA:DNA hybrids
K1 RNase H2
AB 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.
YR 2018
FD 2018-06-29
LK http://hdl.handle.net/10668/12660
UL http://hdl.handle.net/10668/12660
LA en
DS RISalud
RD Apr 9, 2025