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.
This is a preview of subscription content, log in via an institution to check access.
References
Chen, Q., Sun, L. & Chen, Z. J. Nat. Immunol. 17, 1142–1149 (2016).
Li, T. & Chen, Z. J. J. Exp. Med. 215, 1287–1299 (2018).
Motwani, M., Pesiridis, S. & Fitzgerald, K. A. Nat. Rev. Genet. 20, 657–674 (2019).
Crow, Y. J. & Manel, N. Nat. Rev. Immunol. 15, 429–440 (2015).
Uggenti, C. et al. Nat. Genet. https://doi.org/10.1038/s41588-020-00737-3 (2020).
Haag, S. M. et al. Nature 559, 269–273 (2018).
Gentili, M. et al. Cell Rep. 26, 2377–2393.e13 (2019).
Volkman, H. E., Cambier, S., Gray, E. E. & Stetson, D. B. eLife 8, e47491 (2019).
Guey, B. et al. Science 369, 823–828 (2020).
Pathare, G. R. et al. Nature https://doi.org/10.1038/s41586-020-2750-6 (2020).
Michalski, S. et al. Nature https://doi.org/10.1038/s41586-020-2748-0 (2020).
Zhao, B. et al. Nature https://doi.org/10.1038/s41586-020-2749-z (2020).
Boyer, J. A. et al. Science 370, 450–454 (2020).
Kujirai, T. et al. Science 370, 455–458 (2020).
Uggetti, C. et al. Am. J. Neuroradiol. 30, 1971–1976 (2009).
Yu, C.-H. et al. Cell 183, 636–649.e18 (2020).
Sliter, D. A. et al. Nature 561, 258–262 (2018).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41588-020-00746-2
- Springer Nature America, Inc.