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

Abstract

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.

• Authors: Stephanie Jung, Tina von Thülen, Ines Yang, Viktoria Laukemper, Benjamin Rupf, Harshavardhan Janga, Georgios-Dimitrios Panagiotidis, Andreas Schoen, Marina Nicolai, Leon N Schulte, Hannah-Lena Obermann, Friedemann Weber, Andreas Kaufmann, Stefan Bauer
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 48 Issue 18 Pg. 10397-10412 (10 09 2020) ISSN: 1362-4962 [Electronic] England
• PMID: 32946572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chemical References

• Ligands
• Phosphates
• RNA, Ribosomal
• Receptors, Immunologic
• RNA
• Guanosine Triphosphate
• Ribonucleases
• RIGI protein, human
• DEAD Box Protein 58
• RNA Helicases

Topics

• DEAD Box Protein 58 (genetics)
• Guanosine Triphosphate (genetics)
• Humans
• Ligands
• Phosphates (metabolism)
• RNA (chemistry, genetics)
• RNA Helicases (genetics, metabolism)
• RNA, Ribosomal (genetics)
• Receptors, Immunologic
• Ribonucleases (genetics)