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The SKIV2L RNA exosome limits activation of the RIG-I-like receptors.

Eckard, Sterling C; Rice, Gillian I; Fabre, Alexandre; Badens, Catherine; Gray, Elizabeth E; Hartley, Jane L; Crow, Yanick J; Stetson, Daniel B

Nature immunology. 2014;15(9):839-845.

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Abstract

Sensors of the innate immune system that detect intracellular nucleic acids must be regulated to prevent inappropriate activation by endogenous DNA and RNA. The exonuclease Trex1 regulates the DNA-sensing pathway by metabolizing potential DNA ligands that trigger it. However, an analogous mechanism for regulating the RIG-I-like receptors (RLRs) that detect RNA remains unknown. We found here that the SKIV2L RNA exosome potently limited the activation of RLRs. The unfolded protein response (UPR), which generated endogenous RLR ligands through the cleavage of cellular RNA by the endonuclease IRE-1, triggered the production of type I interferons in cells depleted of SKIV2L. Humans with deficiency in SKIV2L had a type I interferon signature in their peripheral blood. Our findings reveal a mechanism for the intracellular metabolism of immunostimulatory RNA, with implications for specific autoimmune disorders.

Bibliographic metadata

Type of resource:
Content type:
Publication status:
Accepted
Publication type:
Published date:
Journal title:
Abbreviated journal title:
ISSN:
Volume:
15
Issue:
9
Start page:
839
End page:
845
Total:
6
Pagination:
839-845
Digital Object Identifier:
10.1038/ni.2948
Pubmed Identifier:
25064072
Pii Identifier:
ni.2948
Attached files embargo period:
Immediate release
Attached files release date:
21st April, 2015
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:230905
Created by:
Crow, Yanick
Created:
10th August, 2014, 14:29:32
Last modified by:
Chase, Diana
Last modified:
21st April, 2015, 16:29:41

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