PMID- 32946572
OWN - NLM
STAT- MEDLINE
DCOM- 20201104
LR  - 20231213
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 48
IP  - 18
DP  - 2020 Oct 9
TI  - A ribosomal RNA fragment with 2',3'-cyclic phosphate and GTP-binding activity 
      acts as RIG-I ligand.
PG  - 10397-10412
LID - 10.1093/nar/gkaa739 [doi]
AB  - 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.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Jung, Stephanie
AU  - Jung S
AD  - Institut fur Immunologie, Philipps-Universitat Marburg, BMFZ, 
      Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
FAU - von Thulen, Tina
AU  - von Thulen T
AD  - Institut fur Immunologie, Philipps-Universitat Marburg, BMFZ, 
      Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
FAU - Yang, Ines
AU  - Yang I
AD  - Institut fur Medizinische Mikrobiologie und Krankenhaushygiene, Medizinische 
      Hochschule Hannover, Carl Neuberg Strasse 1, 30625 Hannover, Germany.
FAU - Laukemper, Viktoria
AU  - Laukemper V
AD  - Institut fur Immunologie, Philipps-Universitat Marburg, BMFZ, 
      Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
FAU - Rupf, Benjamin
AU  - Rupf B
AD  - Institut fur Immunologie, Philipps-Universitat Marburg, BMFZ, 
      Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
FAU - Janga, Harshavardhan
AU  - Janga H
AD  - Institut fur Lungenforschung/iLung, Philipps-Universitat Marburg, BMFZ, 
      Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
FAU - Panagiotidis, Georgios-Dimitrios
AU  - Panagiotidis GD
AD  - Institut fur Virologie, Fachbereich Veterinarmedizin (FB10), 
      Justus-Liebig-Universitat Giessen, Schubertstr. 81, 35392 Giessen, Germany.
FAU - Schoen, Andreas
AU  - Schoen A
AD  - Institut fur Virologie, Fachbereich Veterinarmedizin (FB10), 
      Justus-Liebig-Universitat Giessen, Schubertstr. 81, 35392 Giessen, Germany.
FAU - Nicolai, Marina
AU  - Nicolai M
AD  - Institut fur Immunologie, Philipps-Universitat Marburg, BMFZ, 
      Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
FAU - Schulte, Leon N
AU  - Schulte LN
AD  - Institut fur Lungenforschung/iLung, Philipps-Universitat Marburg, BMFZ, 
      Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
AD  - Deutsches Zentrum fur Lungenforschung (DZL), 35392 Giessen, Germany.
FAU - Obermann, Hannah-Lena
AU  - Obermann HL
AD  - Institut fur Immunologie, Philipps-Universitat Marburg, BMFZ, 
      Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
FAU - Weber, Friedemann
AU  - Weber F
AD  - Institut fur Virologie, Fachbereich Veterinarmedizin (FB10), 
      Justus-Liebig-Universitat Giessen, Schubertstr. 81, 35392 Giessen, Germany.
FAU - Kaufmann, Andreas
AU  - Kaufmann A
AD  - Institut fur Immunologie, Philipps-Universitat Marburg, BMFZ, 
      Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
FAU - Bauer, Stefan
AU  - Bauer S
AD  - Institut fur Immunologie, Philipps-Universitat Marburg, BMFZ, 
      Hans-Meerwein-Strasse 2, 35043 Marburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Ligands)
RN  - 0 (Phosphates)
RN  - 0 (RNA, Ribosomal)
RN  - 0 (Receptors, Immunologic)
RN  - 63231-63-0 (RNA)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 3.1.- (Ribonucleases)
RN  - EC 3.6.1.- (RIGI protein, human)
RN  - EC 3.6.4.13 (DEAD Box Protein 58)
RN  - EC 3.6.4.13 (RNA Helicases)
SB  - IM
MH  - DEAD Box Protein 58/*genetics
MH  - Guanosine Triphosphate/genetics
MH  - Humans
MH  - Ligands
MH  - Phosphates/metabolism
MH  - RNA/chemistry/*genetics
MH  - RNA Helicases/*genetics/metabolism
MH  - RNA, Ribosomal/*genetics
MH  - Receptors, Immunologic
MH  - Ribonucleases/genetics
PMC - PMC7544222
EDAT- 2020/09/19 06:00
MHDA- 2020/11/05 06:00
PMCR- 2020/09/18
CRDT- 2020/09/18 17:12
PHST- 2020/08/26 00:00 [accepted]
PHST- 2020/08/19 00:00 [revised]
PHST- 2019/10/31 00:00 [received]
PHST- 2020/09/19 06:00 [pubmed]
PHST- 2020/11/05 06:00 [medline]
PHST- 2020/09/18 17:12 [entrez]
PHST- 2020/09/18 00:00 [pmc-release]
AID - 5908532 [pii]
AID - gkaa739 [pii]
AID - 10.1093/nar/gkaa739 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2020 Oct 9;48(18):10397-10412. doi: 10.1093/nar/gkaa739.