Defining the functional determinants for RNA surveillance by RIG‐I

Kohlway, Andrew; Luo, Dahai; Rawling, David; Ding, Sheng; Pyle, Anna Marie

doi:10.1038/embor.2013.108

Cited by 101 publications

(202 citation statements)

References 31 publications

(56 reference statements)

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“…Further, RIG-I also displays no intermolecular cooperativity for RNA binding, prefers short RNA, including 10 base pair hairpins and siRNA, for its enzymatic activity, and can be effectively stimulated by short and long RNA with respect to IFN production. 30 Finally, in all known RIG-I:dsRNA complexes, RIG-I was crystallized at the ends of all RNA duplexes of different length and sequence composition, even in the absence of the CTD domain (Fig. 3), further suggesting that RIG-I preferentially binds at the duplex RNA terminus.…”

Section: Rig-i Prefers Capping the Ends Of Rna Duplex Rather Than Binmentioning

confidence: 99%

“…1A), ATP hydrolysis, and cell-based IFN production. 30 Interestingly, new evidence from EM studies in the Hur lab suggests that, despite the lack of cooperativity, internal binding could be induced by a nucleation effect initiated by RIG-I capping at the end of the RNA duplex, which could lead to a more robust interferon response. 35,36 Conceivably, at lower concentrations of RIG-I in the resting state, RIG-I surveys and binds only the ends of 5′trisphor-phylated RNA, but upon IFN induction and the concomitant increase in cellular levels of RIG-I protein, RIG-I molecules may start to bind internally near the RIG-I-capped RNA.…”

Section: Rig-i Prefers Capping the Ends Of Rna Duplex Rather Than Binmentioning

confidence: 99%

“…30 Indeed, our recent work allowed us to define the consensus, minimal functional RNA PAMP for RIG-I. It is clear that RIG-I requires only the 5′ terminus of duplex RNA, along with an adjacent 10-12 base pairs for binding (Fig.…”

Section: Rig-i Prefers Capping the Ends Of Rna Duplex Rather Than Binmentioning

confidence: 99%

“…This design allows RIG-I to examine the correct chemistry and structure of the RNA ligand. [30][31][32][33] …”

Section: Rig-i: Two-component Molecular Machine For Sensing and Respomentioning

confidence: 99%

“…Interestingly, there are two opposing functional surfaces on HEL2i: one RNA binding surface with a conserved residue (Q511 in human RIG-I) that dynamically samples the RNA ligand ( Figs. 1 and 3) 30 and one inhibitory surface that interacts with the CARD2 domain to maintain the auto-inhibited state of RIG-I.…”

Section: Rig-i: Two-component Molecular Machine For Sensing and Respomentioning

confidence: 99%

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Toward a crystal-clear view of the viral RNA sensing and response by RIG-I-like receptors

Luo

2014

RNA Biology

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Section: Rig-i Prefers Capping the Ends Of Rna Duplex Rather Than Binmentioning

confidence: 99%

Section: Rig-i Prefers Capping the Ends Of Rna Duplex Rather Than Binmentioning

confidence: 99%

Section: Rig-i Prefers Capping the Ends Of Rna Duplex Rather Than Binmentioning

confidence: 99%

“…This design allows RIG-I to examine the correct chemistry and structure of the RNA ligand. [30][31][32][33] …”

Section: Rig-i: Two-component Molecular Machine For Sensing and Respomentioning

confidence: 99%

Section: Rig-i: Two-component Molecular Machine For Sensing and Respomentioning

confidence: 99%

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Toward a crystal-clear view of the viral RNA sensing and response by RIG-I-like receptors

Luo

2014

RNA Biology

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Structure‐guided design of immunomodulatory RNAs specifically targeting the cytoplasmic viral RNA sensor RIG‐I

Yong

Zheng

et al. 2019

FEBS Letters

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The cytoplasmic immune sensor RIG‐I detects viral RNA and initiates an antiviral immune response upon activation. It has become a potential target for vaccination and immunotherapies. To develop the smallest but potent immunomodulatory RNA (immRNAs) species, we performed structure‐guided RNA design and used biochemical, structural, and cell‐based methods to select and characterize the immRNAs. We demonstrated that inserting guanosine at position 9 to the 10mer RNA hairpin (3p10LG9) activates RIG‐I more robustly than the parental RNA. 3p10LG9 interacts strongly with the RIG‐I helicase‐CTD RNA sensing module and disrupts the auto‐inhibitory interaction between the HEL2i and CARDs domains. We further showed that 3p10LA9 has a stronger cellular activity than 3p10LG9. Collectively, purine insertion at position 9 of the immRNA species triggered more robust activation of RIG‐1.

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RIG ‐ I ‐Like Receptors

Yong

Luo

2015

Encyclopedia of Life Sciences

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The RIG‐I‐like receptors (RLRs), RIG‐I (retinoic acid inducible gene 1), MDA5 (melanoma differentiation‐associated gene 5) and LGP2 (laboratory of genetics and physiology 2) play an essential role in sensing viral infection and initiating interferon‐mediated antiviral immune response. RLRs share similar domain architecture to support specific detection of viral RNA (ribonucleic acid). RIG‐I has an auto‐inhibitory conformation and upon binding of RNA ligand undergoes conformational changes to expose N ‐terminal CARDs (caspase activation and recruitment domains) for interaction with the adaptor protein MAVS (mitochondrial antiviral‐signalling protein) for signalling. MDA5 adopts an open but inactive conformation and is able to oligomerise on long RNA duplexes to bring its CARDs into close proximity to MAVS. The downstream signalling cascade up‐regulates the type I interferon expression. Post‐translational modifications, alternative splicing and translational variants as well as several regulatory proteins play important roles in the regulation of RLRs signalling. Although robust activation of RLRs is essential for clearance of viral infection, uncontrolled activation of RLR signalling could potentially trigger or exacerbate pre‐existing autoimmune conditions. Key Concepts RIG‐I‐like receptors (RLRs) are pattern recognition receptor (PRR) which specifically recognise viral RNAs RLRs undergo conformational changes leading to activation when bound to viral RNA RLRs relay signal to a common signalling adaptor MAVS (mitochondrial antiviral‐signalling protein) leading to activation of transcription factors promoting the expression of interferons and pro‐inflammatory cytokines which reduces initial viral replication and spread RLRs are tightly regulated by various proteins and post‐translational modifications to prevent undesired auto‐activation

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Defining the functional determinants for RNA surveillance by RIG‐I

Abstract: Defining the functional determinants for RNA surveillance by RIG-IThis study shows that HEL2i-domain mediated scanning allows RIG-I to sense the length of RNA targets, and a short RNA duplex that binds one RIG-I molecule can stimulate ATPase activity and interferon response.

Cited by 101 publications

References 31 publications

Toward a crystal-clear view of the viral RNA sensing and response by RIG-I-like receptors

Toward a crystal-clear view of the viral RNA sensing and response by RIG-I-like receptors

Structure‐guided design of immunomodulatory RNAs specifically targeting the cytoplasmic viral RNA sensor RIG‐I

RIG ‐ I ‐Like Receptors

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