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Cell Rep. 2019 Feb 19;26(8):2019-2027.e4. doi: 10.1016/j.celrep.2019.01.107.

RIG-I Selectively Discriminates against 5'-Monophosphate RNA.

Author information

1
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.
2
Department of Immunobiology, Yale University, New Haven, CT 06520, USA.
3
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Department of Immunobiology, Yale University, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.
4
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA. Electronic address: anna.pyle@yale.edu.

Abstract

The innate immune sensor RIG-I must sensitively detect and respond to viral RNAs that enter the cytoplasm, while remaining unresponsive to the abundance of structurally similar RNAs that are the products of host metabolism. In the case of RIG-I, these viral and host targets differ by only a few atoms, and a molecular mechanism for such selective differentiation has remained elusive. Using a combination of quantitative biophysical and immunological studies, we show that RIG-I, which is normally activated by duplex RNAs containing a 5'-tri- or diphosphate (5'-ppp or 5'-pp RNAs), is actively antagonized by RNAs containing 5'-monophosphates (5'-p RNAs). This is accomplished by a gating mechanism in which an alternative RIG-I conformation blocks the C-terminal domain (CTD) upon 5'-p RNA binding, thereby short circuiting the activation of signaling.

KEYWORDS:

PRR; RIG-I receptor; antiviral; autoimmunity; host-pathogen; innate immunity; interferon; pattern recognition receptor

PMID:
30784585
DOI:
10.1016/j.celrep.2019.01.107
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