5'-Triphosphate RNA Is the Ligand for RIG-I

  title={5'-Triphosphate RNA Is the Ligand for RIG-I},
  author={Veit Hornung and Jana M. Ellegast and Sarah Kim and Krzysztof Brzózka and Andreas Jung and Hiroki Kato and Hendrik Poeck and Shizuo Akira and Karl-Klaus Conzelmann and Martin Schlee and Stefan Endres and Gunther Hartmann},
  pages={994 - 997}
The structural basis for the distinction of viral RNA from abundant self RNA in the cytoplasm of virally infected cells is largely unknown. We demonstrated that the 5′-triphosphate end of RNA generated by viral polymerases is responsible for retinoic acid–inducible protein I (RIG-I)–mediated detection of RNA molecules. Detection of 5′-triphosphate RNA is abrogated by capping of the 5′-triphosphate end or by nucleoside modification of RNA, both occurring during posttranscriptional RNA processing… 

5′-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I

It is shown that RIG-I ligands require base-paired structures in conjunction with a free 5′-triphosphate to trigger antiviral signaling, and accurately defines a minimal molecular pattern sufficient to activate Rig-I that can be found in viral genomes or transcripts.

Cytosolic 5′-Triphosphate Ended Viral Leader Transcript of Measles Virus as Activator of the RIG I-Mediated Interferon Response

RIG-I is proposed to recognize Mononegavirales transcription, which occurs in the cytosol, while scanning cytosolic RNAs, and to trigger an IFN response when encountering a free 5′-triphosphate RNA resulting from a mislocated transcription activity, which is therefore considered as the hallmark of a foreign invader.

Cytosolic Viral Sensor RIG-I Is a 5'-Triphosphate–Dependent Translocase on Double-Stranded RNA

Using single-molecule protein-induced fluorescence enhancement, a robust adenosine 5′-triphosphate–powered dsRNA translocation activity of RIG-I is discovered and may provide a means to specifically sense and counteract replicating viruses.

A conserved isoleucine in the binding pocket of RIG-I controls immune tolerance to mitochondrial RNA

This study demonstrates that avoidance of 5’p-RNA recognition is crucial to preventing mtRNA-triggered RIG-I-mediated autoinflammation.

Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I mediated immunity

The findings reveal that antiviral immunity can be triggered by host RNAs that are unshielded following depletion of their respective binding proteins by the virus.

5'-Triphosphate-Dependent Activation of PKR by RNAs with Short Stem-Loops

It is reported that RNAs with very limited secondary structures activate PKR in a 5′-triphosphate–dependent fashion in vitro and in vivo, and this form of RNA-based discrimination may be a critical step in mounting an early immune response.



Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses

It is found that RIG-I is essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza virus and Japanese encephalitis virus, whereas MDA5 is critical for picornavirus detection.

The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses

Intracellular double-stranded RNA (dsRNA) is a chief sign of replication for many viruses. Host mechanisms detect the dsRNA and initiate antiviral responses. In this report, we identify retinoic acid

RNA-guided Nucleotide Modification of Ribosomal and Other RNAs*

Key developments include: identification of new guide RNAs that reside in mammalian Cajal bodies (these RNAs are specific for the four snRNAs transcribed by RNA polymerase II (pol II), which are thought to undergo maturation and possibly RNP assembly at this location (11); and evidence that the trypanosome transspliced leader is a substrate for guided modification.

A structural basis for discriminating between self and nonself double-stranded RNAs in mammalian cells

It is shown that the recognition of siRNAs is mediated by the RNA helicase RIG-I and that the presence of 3′ overhangs impairs its ability to unwind the dsRNA substrate and activate downstream signaling to the transcription factor IRF-3.

A protein covalently linked to poliovirus genome RNA.

The data show that the genome of poliov virus, but not poliovirus mRNA, is covalently attached to a small virus-coded protein (molecular weight less than 7000), which is called VPg, which is probably linked to the 5' end of the polio genome.

Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus.

It is shown that mda-5 is the dominant receptor mediating type I IFN secretion in response to polyI:C in vitro and in vivo, and selectively impaired antiviral response to encephalomyocarditis picornavirus is exhibited, indicating functional specialization of mda -5 in vivo.

The RNA Helicase Lgp2 Inhibits TLR-Independent Sensing of Viral Replication by Retinoic Acid-Inducible Gene-I1

It is proposed that Lgp2 acts as a negative feedback regulator of antiviral signaling by sequestering dsRNA from RIG-I, and inhibits SV and Newcastle disease virus signaling to IFN-stimulated regulatory element- and NF-κB-dependent pathways.

Gamma-monomethyl phosphate: a cap structure in spliceosomal U6 small nuclear RNA.

  • R. SinghR. Reddy
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1989
The cap structure of human U6 snRNA is characterized and shows that the gamma phosphate of the 5' guanosine triphosphate is methylated, distinct from all other cap structures characterized thus far.

Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase

An improved method for T7 siRNA synthesis is described that alleviates the interferon response while maintaining full efficacy of the siRNAs.

Regulating Intracellular Antiviral Defense and Permissiveness to Hepatitis C Virus RNA Replication through a Cellular RNA Helicase, RIG-I

It is shown that structured hepatitis C virus (HCV) genomic RNA activates interferon regulatory factor 3 (IRF3), thereby inducing Interferon in cultured cells, and RIG-I is a pathogen receptor that regulates cellular permissiveness to HCV replication and may play a key role inInterferon-based therapies for the treatment of HCV infection.