Science and Research

A ribosomal RNA fragment with 2',3'-cyclic phosphate and GTP-binding activity acts as RIG-I ligand

The RNA helicase RIG-I plays a key role in sensing pathogen-derived RNA. Double-stranded RNA structures bearing 5'-tri- or diphosphates are commonly referred to as activating RIG-I ligands. However, endogenous RNA fragments generated during viral infection via RNase L also activate RIG-I. Of note, RNase-digested RNA fragments bear a 5'-hydroxyl group and a 2',3'-cyclic phosphate. How endogenous RNA fragments activate RIG-I despite the lack of 5'-phosphorylation has not been elucidated. Here we describe an endogenous RIG-I ligand (eRL) that is derived from the internal transcribed spacer 2 region (ITS2) of the 45S ribosomal RNA after partial RNase A digestion in vitro, RNase A protein transfection or RNase L activation. The immunostimulatory property of the eRL is dependent on 2',3'-cyclic phosphate and its sequence is characterized by a G-quadruplex containing sequence motif mediating guanosine-5'-triphosphate (GTP) binding. In summary, RNase generated self-RNA fragments with 2',3'-cyclic phosphate function as nucleotide-5'-triphosphate binding aptamers activating RIG-I.

  • Jung, S.
  • von Thulen, T.
  • Yang, I.
  • Laukemper, V.
  • Rupf, B.
  • Janga, H.
  • Panagiotidis, G. D.
  • Schoen, A.
  • Nicolai, M.
  • Schulte, L. N.
  • Obermann, H. L.
  • Weber, F.
  • Kaufmann, A.
  • Bauer, S.
Publication details
DOI: 10.1093/nar/gkaa739
Journal: Nucleic Acids Res
Work Type: Original
Location: BREATH, UGMLC
Disease Area: PH
Partner / Member: JLU, MHH, UMR
Access-Number: 32946572
See publication on PubMed

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