PuSH - Publication Server of Helmholtz Zentrum München

Jung, S. ; von Thülen, 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.*

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

Nucleic Acids Res. 48, 10397-10412 (2020)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag

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.

Altmetric
Additional Metrics?
Tags
statConAck
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Quellenangaben Volume: 48, Issue: 18, Pages: 10397-10412 Article Number: , Supplement: ,
Publisher Oxford University Press
Reviewing status Peer reviewed
Grants European Commission
German Academic Scholarship Foundation
German Research Foundation (DFG)
German Center for Infection Research (DZIF)