The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands

Wang, Wenshuai; Pyle, Anna Marie

doi:10.1016/j.molcel.2022.09.029

Cited by 27 publications

(29 citation statements)

References 72 publications

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“…In contrast to LGP2, RIG-I and MDA5 share two caspase-activation and recruitment domains (CARDs) at their N-terminus that triggers downstream signaling events [ 2 , 7 ]. In case of RIG-I these CARDs are intramolecularly bound by the helicase domain and CTD, provoking a closed conformation of the protein and thereby preventing downstream signaling in absent of a ligand [ 7 , 25 ]. Nucleic acid recognition entails the hydrolysis of ATP by RIG-I and provokes the change to an open conformation and its oligomerization.…”

Section: The Classical Pathogen Recognition Receptorsmentioning

confidence: 99%

“…Such domain crosstalk is well imaginable for the IFN-regulated PARPs as well. Another mode of activation, although highly speculative at present, might be comparable to how RIG-I is activated [ 25 ]. The RRMs and the long intrinsically disordered glycine-rich region present in PARP10 and PARP14 might contribute to an inactive conformation, which opens when the proteins interact with RNA ( Figure 3 ).…”

Section: The Ifn-regulated Subclass Of Parpsmentioning

confidence: 99%

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IFN-Induced PARPs—Sensors of Foreign Nucleic Acids?

2023

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Cells have developed different strategies to cope with viral infections. Key to initiating a defense response against viruses is the ability to distinguish foreign molecules from their own. One central mechanism is the perception of foreign nucleic acids by host proteins which, in turn, initiate an efficient immune response. Nucleic acid sensing pattern recognition receptors have evolved, each targeting specific features to discriminate viral from host RNA. These are complemented by several RNA-binding proteins that assist in sensing of foreign RNAs. There is increasing evidence that the interferon-inducible ADP-ribosyltransferases (ARTs; PARP9—PARP15) contribute to immune defense and attenuation of viruses. However, their activation, subsequent targets, and precise mechanisms of interference with viruses and their propagation are still largely unknown. Best known for its antiviral activities and its role as RNA sensor is PARP13. In addition, PARP9 has been recently described as sensor for viral RNA. Here we will discuss recent findings suggesting that some PARPs function in antiviral innate immunity. We expand on these findings and integrate this information into a concept that outlines how the different PARPs might function as sensors of foreign RNA. We speculate about possible consequences of RNA binding with regard to the catalytic activities of PARPs, substrate specificity and signaling, which together result in antiviral activities.

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Section: The Classical Pathogen Recognition Receptorsmentioning

confidence: 99%

Section: The Ifn-regulated Subclass Of Parpsmentioning

confidence: 99%

IFN-Induced PARPs—Sensors of Foreign Nucleic Acids?

2023

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“…These structures revealed that RIG-I utilizes two different conformations to distinguish viral and host dsRNA. 1 This finding was achieved by collecting cryo-EM data from samples in the presence of viral or host dsRNAs, followed by data processing designed to isolate different conformations within the same dataset. The protocol below describes the sample preparation of making complexes of RIG-I and dsRNAs in the presence of ATP and Mg 2+ , followed by grid freezing.…”

Section: Before You Beginmentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Wang and Pyle (2022). 1 …”

mentioning

confidence: 99%

A protocol for capturing RNA-sensing innate immune receptors in multiple conformations by single-particle cryo-EM

Wang¹,

Fedorova²,

Pyle³

2023

STAR Protocols

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“…1,2 Studies have shown that both 5'-triphosphate (p3dsRNA) and 5'-diphosphate (p2dsRNA) are potent agonists for the RIG-I receptor, with p2dsRNA being the primary RNA requirement for activation of RIG-I. 3,4,5 Until recently, RIG-I had never been captured in complex with p2dsRNA, most likely due to the lack of commercially available 5'-diphophate RNA ligands. The generation of 5'pp-RNA from chemically synthesized 5'ppp-RNA has previously been described, involving incubation of the 5'ppp-RNA with vaccinia virus capping enzyme in the absence of GTP and S-adenosyl methionine.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, deprotection, and purification of diphosphorylated RNA oligonucleotides.

Fergione

Fedorova

Pyle

2023

Preprint

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In this technical note, we systematically describe the chemical synthesis, deprotection, and purification of diphosphorylated RNA oligonucleotides. This process eliminates the need for an enzymatic step after chemical synthesis of a 5’triphosphate RNA, allowing the user to synthesize the 5’diphosphate RNA directly. This protocol can also be applied to other chemically synthesized nucleic acids, including those with modifications.

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The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands

Cited by 27 publications

References 72 publications

IFN-Induced PARPs—Sensors of Foreign Nucleic Acids?

IFN-Induced PARPs—Sensors of Foreign Nucleic Acids?

A protocol for capturing RNA-sensing innate immune receptors in multiple conformations by single-particle cryo-EM

Synthesis, deprotection, and purification of diphosphorylated RNA oligonucleotides.

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