5'-triphosphate-dependent activation of PKR by RNAs with short stem-loops.
Molecular patterns in pathogenic RNAs can be recognized by the innate immune system, and a component of this response is the interferon-induced enzyme RNA-activated protein kinase (PKR). The major activators of PKR have been proposed to be long double-stranded RNAs. We report that RNAs with very limited secondary structures activate PKR in a 5'-triphosphate-dependent fashion in vitro and in vivo. Activation of PKR by 5'-triphosphate RNA is independent of RIG-I and is enhanced by treatment with type 1 interferon (IFN-alpha). Surveillance of molecular features at the 5' end of transcripts by PKR presents a means of allowing pathogenic RNA to be distinguished from self-RNA. The evidence presented here suggests that this form of RNA-based discrimination may be a critical step in mounting an early immune response.
Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.
Subba Rao
SR
Nallagatla
Jungwook
J
Hwang
Rebecca
R
Toroney
Xiaofeng
X
Zheng
Craig E
CE
Cameron
Philip C
PC
Bevilacqua
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004789:Enzyme Activation; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011122:Polyphosphates / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D014162:Transfection; D014709:Vero Cells; D019892:eIF-2 Kinase / Q000378:metabolism*
D015852:Eukaryotic Initiation Factor-2; D016898:Interferon-alpha; D011122:Polyphosphates; D012330:RNA, Double-Stranded; D011971:Receptors, Immunologic; D012313:RNA; D016899:Interferon-beta; D019892:eIF-2 Kinase; D010744:Phosphoric Monoester Hydrolases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; C005692:triphosphoric acid