Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters

Database
Language
Journal
Affiliation country
Publication year range
1.
EMBO J ; 37(15)2018 08 01.
Article in English | MEDLINE | ID: mdl-29959219

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.


Subject(s)
Autoimmune Diseases of the Nervous System/genetics , Long Interspersed Nucleotide Elements/genetics , Nervous System Malformations/genetics , Ribonuclease H/genetics , Cell Line, Tumor , Gene Knockout Techniques , HCT116 Cells , HeLa Cells , Humans , Reverse Transcription/genetics , Ribonuclease H/biosynthesis
SELECTION OF CITATIONS
SEARCH DETAIL