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Loosening the grip on nuclear cGAS

Maintaining ignorance to self-nucleic acids can prevent inflammatory diseases such as Aicardi–Goutières syndrome (AGS). A new study finds that mutations in LSM11 and RNU7-1, which encode components of the histone messenger RNA–preprocessing complex, cause AGS by loosening the binding of cyclic GMP–AMP synthase (cGAS) to nucleosomes, thus enabling cGAS activation and induction of type I interferons.

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Fig. 1: U7 alterations in AGS8/9 promote cGAS activation.

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Correspondence to Katherine A. Fitzgerald.

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Humphries, F., Fitzgerald, K.A. Loosening the grip on nuclear cGAS. Nat Genet 52, 1269–1270 (2020). https://doi.org/10.1038/s41588-020-00746-2

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