RIG-I ATPase activity and discrimination of self-RNA versus non-self-RNA

MBio
Stéphanie AnchisiDominique Garcin

Abstract

Many RNA viruses are detected by retinoic acid-inducible gene i (RIG-I), a cytoplasmic sensor that triggers an antiviral response upon binding non-self-RNA that contains a stretch of double-stranded RNA (dsRNA) bearing a base-paired 5' ppp nucleotide. To gain insight into how RIG-I discriminates between self-RNA and non-self-RNA, we used duplexes whose complementary bottom strand contained both ribo- and deoxynucleotides. These duplexes were examined for their binding to RIG-I and their relative abilities to stimulate ATPase activity, to induce RIG-I dimerization on the duplex, and to induce beta interferon (IFN-β) expression. We show that the chemical nature of the bottom strand is not critical for RIG-I binding. However, two key ribonucleotides, at positions 2 and 5 on the bottom strand, are minimally required for the RIG-I ATPase activity, which is necessary but not sufficient for IFN-β stimulation. We find that duplexes with shorter stretches of dsRNA, as model self-RNAs, bind less stably to RIG-I but nevertheless have an enhanced ability to stimulate the ATPase. Moreover, ATPase activity promotes RIG-I recycling on RIG-I/dsRNA complexes. Since pseudo-self-RNAs bind to RIG-I less stably, they are preferentially recycled by ...Continue Reading

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Citations

Feb 10, 2016·Current Opinion in Structural Biology·Jungsan Sohn, Sun Hur
Nov 28, 2015·Nucleic Acids Research·Anand RamanathanSmita S Patel
Apr 4, 2015·Molecular Cell·Daniel Kolakofsky, Dominique Garcin
Jul 15, 2015·Cytokine·Friedemann Weber
Apr 16, 2017·The Journal of Biological Chemistry·Charlotte Lässig, Karl-Peter Hopfner
Jun 22, 2020·Immunological Reviews·Hongyu Lin, Xuetao Cao
Jan 18, 2017·Frontiers in Immunology·Yiliu LiuRongtuan Lin
Aug 6, 2019·Frontiers in Immunology·Morgan Brisse, Hinh Ly
Jan 24, 2021·Seminars in Cancer Biology·Mohammad Imran KhanHasan Mukhtar
Feb 27, 2016·Current Opinion in Structural Biology·Daisy W Leung, Gaya K Amarasinghe
Oct 17, 2017·Biochemical and Biophysical Research Communications·Masahiko Miyamoto, Akihiko Komuro

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Methods Mentioned

BETA
pulldown
transfection
flow cytometry
electrophoretic mobility shift
PCR
in vitro transcription

Software Mentioned

CFlow Plus
ImageQuantTL
GraphPad
Accuri
GraphPad Prism
ImageJ

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