MRC Human Genetics Unit
Medical Research Council Human Genetics Unit

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RNase H2 promotes LINE-1 retrotransposition

Research challenges prior model of immune activation in Aicardi-Goutieres syndrome

Diagrammatic synposis of RNAseH2 role in LINE1 retrostransposition

Retrotransposons are pieces of DNA that can make additional copies of themselves which are insert back into DNA. Retrotransposon DNA forms a large proportion of the complete set of DNA, or genome, of most mammals. Human genomes are thought to contain active LINE‐1 (L1) elements which can still copy themselves and move around the genome. These LINE-1 elements have been linked to Aicardi‐Goutières syndrome (AGS), which can cause brain changes, such as microcephaly, or small brain size, due to an inflammatory response. Protein that are known to repress the movement of LINE-1 elements have been found to be mutated in AGS.

Jose Garcia-Perez and colleagues at the Universities of Edinburgh and Granada explored the hypothesis that increased LINE‐1 activity may be the cause of immune activation in AGS. Contrary to this model, they found that cells without RNAse H2, an enzyme frequently mutated in AGS, actually had less movement of LINE-1 elements. If amounts of RNAse H2 are artificially increased, there is increased movement of LINE-1 elements. The work helps further the mechanistic understanding of LINE-1 retrotransposition, but appears to be inconsistent with the concept that LINE‐1‐derived nucleic acids drive autoinflammation in AGS. 

Links

Jose Garcia Perez research group

Andrew Jackson research group

Original article: https://doi.org/10.15252/embj.201798506