Immune Netw.  2016 Aug;16(4):249-255. 10.4110/in.2016.16.4.249.

Dependence of RIG-I Nucleic Acid-Binding and ATP Hydrolysis on Activation of Type I Interferon Response

• Baek YM
• Yoon S
• Hwang YE
• Kim DE

• KMID: 2349886
• DOI: http://doi.org/10.4110/in.2016.16.4.249

Abstract

Exogenous nucleic acids induce an innate immune response in mammalian host cells through activation of the retinoic acid-inducible gene I (RIG-I). We evaluated RIG-I protein for RNA binding and ATPase stimulation with RNA ligands to investigate the correlation with the extent of immune response through RIG-I activation in cells. RIG-I protein favored blunt-ended, double-stranded RNA (dsRNA) ligands over sticky-ended dsRNA. Moreover, the presence of the 5'-triphosphate (5'-ppp) moiety in dsRNA further enhanced binding affinity to RIG-I. Two structural motifs in RNA, blunt ends in dsRNA and 5'-ppp, stimulated the ATP hydrolysis activity of RIG-I. These structural motifs also strongly induced IFN expression as an innate immune response in cells. Therefore, we suggest that IFN induction through RIG-I activation is mainly determined by structural motifs in dsRNA that increase its affinity for RIG-I protein and stimulate ATPase activity in RIG-I.

Keyword

Retinoic acid inducible gene I (RIG-I); Interferon induction; 5'-terminal triphosphate; ATP hydrolysis; RNA binding

MeSH Terms

Adenosine Triphosphatases
Adenosine Triphosphate*
Hydrolysis*
Immunity, Innate
Interferon Type I*
Ligands
Nucleic Acids
RNA
RNA, Double-Stranded
Adenosine Triphosphatases
Adenosine Triphosphate
Interferon Type I
Ligands
Nucleic Acids
RNA
RNA, Double-Stranded