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Nucleic Acids Res. 2017 Feb 17;45(3):1442-1454. doi: 10.1093/nar/gkw816.

Selective RNA targeting and regulated signaling by RIG-I is controlled by coordination of RNA and ATP binding.

Author information

1
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
2
Howard Hughes Medical Institute, Chevy Chase, MD, USA.
3
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA

Abstract

RIG-I is an innate immune receptor that detects and responds to infection by deadly RNA viruses such as influenza, and Hepatitis C. In the cytoplasm, RIG-I is faced with a difficult challenge: it must sensitively detect viral RNA while ignoring the abundance of host RNA. It has been suggested that RIG-I has a ‘proof-reading’ mechanism for rejecting host RNA targets, and that disruptions of this selectivity filter give rise to autoimmune diseases. Here, we directly monitor RNA proof-reading by RIG-I and we show that it is controlled by a set of conserved amino acids that couple RNA and ATP binding to the protein (Motif III). Mutations of this motif directly modulate proof-reading by eliminating or enhancing selectivity for viral RNA, with major implications for autoimmune disease and cancer. More broadly, the results provide a physical explanation for the ATP-gated behavior of SF2 RNA helicases and receptor proteins.

PMID:
28180316
PMCID:
PMC5388420
DOI:
10.1093/nar/gkw816
[Indexed for MEDLINE]
Free PMC Article

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