RIG-I-Like Receptors Evolved Adaptively in Mammals, with Parallel Evolution at LGP2 and RIG-I

Cagliani, Rachele; Forni, Diego; Tresoldi, Claudia; Filippi, Giulia; Rainone, Veronica; Gioia, Luca De; Clerici, Mario; Sironi, Manuela

doi:10.1016/j.jmb.2013.10.040

Cited by 29 publications

(33 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this hypothesis, two groups reported that PKR has a strong signature of positive selection (21,22). Similar findings of positive selection have been found for retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) (23), revealing that multiple dsRNA sensors have been engaged in arms races with viruses. In the case of PKR, rapidly evolving codons were identified in both the N-terminal half of PKR (though not in the dsRNA-binding residues) and throughout the C-terminal kinase domain, consistent with multiple regions of PKR being targets of viral antagonists (21,22).…”

Section: Pkr Versus Viral Antagonists: Evolutionary Signatures Of Consupporting

confidence: 58%

An Evolutionary View of the Arms Race between Protein Kinase R and Large DNA Viruses

Carpentier

Geballe

2016

J Virol

View full text Add to dashboard Cite

bTo establish productive infections, viruses must counteract numerous cellular defenses that are poised to recognize viruses as nonself and to activate antiviral pathways. The opposing goals of host and viral factors lead to evolutionary arms races that can be illuminated by evolutionary and computational methods and tested in experimental models. Here we illustrate how this perspective has been contributing to our understanding of the interactions of the protein kinase R pathway with large DNA viruses.

show abstract

Section: Pkr Versus Viral Antagonists: Evolutionary Signatures Of Consupporting

confidence: 58%

An Evolutionary View of the Arms Race between Protein Kinase R and Large DNA Viruses

Carpentier

Geballe

2016

J Virol

View full text Add to dashboard Cite

show abstract

“…Retinoic acid-inducible gene (RIG)-1 like receptors (RLRs) are a group of PRRs that recognize viral nucleic acids and trigger an inflammatory response. Two major RLRs, RIG-1 encoded by the ddx58 gene in vertebrates and MDA5 (melanoma differentiation associated protein 5) with DExD/H Box, are pivotal viral RNA sensors and able to detect long and short fragments of dsRNA, respectively [49]. Both RLRs are cytosolic ATP dependent RNA helicases composed of a N-terminal caspase recruitment domain (CARD), followed by the helicase domain and a C-terminal viral RNA-binding domain.…”

Section: Rig-1-like Receptors and Responses Targeting Viral Rnamentioning

confidence: 99%

Transcriptome analysis reveals strong and complex antiviral response in a mollusc

He¹,

Jouaux²,

Ford³

et al. 2015

Fish & Shellfish Immunology

123

139

View full text Add to dashboard Cite

“…Similar in structure and function, these proteins share significant sequence homologies that define them as the products of an evolutionarily conserved gene family (8) (Fig. 1A).…”

mentioning

confidence: 99%

MDA5 and LGP2: Accomplices and Antagonists of Antiviral Signal Transduction

Rodriguez

Bruns

Horvath

2014

J Virol

105

View full text Add to dashboard Cite

Mammalian cells have the ability to recognize virus infection and mount a powerful antiviral transcriptional response that provides an initial barrier to replication and impacts both innate and adaptive immune responses. Retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) proteins mediate intracellular virus recognition and are activated by viral RNA ligands to induce antiviral signal transduction. While the mechanisms of RIG-I regulation are already well understood, less is known about the more enigmatic melanoma differentiation-associated 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2). Emerging evidence suggests that these two RLRs are intimately associated as both accomplices and antagonists of antiviral signal transduction.C ellular antiviral signaling is initiated following recognition of virus-encoded molecular signatures, often in the form of nucleic acids. Infection by RNA viruses results in cytosolic accumulation of double-stranded RNA (dsRNA) or otherwise chemically distinct, non-self RNA species. Sentry proteins in the cytoplasm recognize characteristics of non-self RNAs and can trigger downstream signal transduction pathways that culminate in activated antiviral transcription regulators (1-3). These factors accumulate in the nucleus, where they drive the expression of virus-induced genes, including the primary antiviral cytokine, beta interferon (IFN-␤), and diverse direct and indirect antiviral effectors (4).One group of intracellular responders, the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), includes the proteins RIG-I (5), melanoma differentiation-associated 5 (MDA5) (6), and laboratory of genetics and physiology 2 (LGP2) (7). Similar in structure and function, these proteins share significant sequence homologies that define them as the products of an evolutionarily conserved gene family (8) (Fig. 1A). The RLR proteins are thought to share the ability to detect molecular signatures of virus infection and activate antiviral signaling cascades, but they differ in both their RNA recognition capacities and signaling properties (9, 10). RIG-I, MDA5, and LGP2 share homologous DECH box helicase domain regions that have intrinsic dsRNA binding and ATP hydrolysis functions and a C-terminal domain that has been implicated in binding to RNA termini and autoregulation (11-13). RIG-I and MDA5 both have tandem N-terminal caspase activation and recruitment domain (CARD) motifs, protein interaction domains that mediate associations with upstream and downstream regulatory machinery. The CARDs are regulated by posttranslational modifications, including ubiquitination and phosphorylation (14-16). Current evidence indicates that RNA recognition by RIG-I and MDA5 is accompanied by CARD dephosphorylation, enabling their productive interaction with signaling machinery. Much of the knowledge of the RLR signaling pathway was developed by detailed study of RIG-I, the prototype RLR (17), and investigations of MDA5 have contributed greatly to a general paradigm for RLR signaling (Fig. 1...

show abstract

RIG-I-Like Receptors Evolved Adaptively in Mammals, with Parallel Evolution at LGP2 and RIG-I

Cited by 29 publications

References 68 publications

An Evolutionary View of the Arms Race between Protein Kinase R and Large DNA Viruses

An Evolutionary View of the Arms Race between Protein Kinase R and Large DNA Viruses

Transcriptome analysis reveals strong and complex antiviral response in a mollusc

MDA5 and LGP2: Accomplices and Antagonists of Antiviral Signal Transduction

Contact Info

Product

Resources

About