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LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA
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dc.contributor.author | Childs, Kay S. | |
dc.contributor.author | Randall, Richard E. | |
dc.contributor.author | Goodbourn, Stephen | |
dc.date.accessioned | 2014-07-16T14:31:04Z | |
dc.date.available | 2014-07-16T14:31:04Z | |
dc.date.issued | 2013-05-09 | |
dc.identifier | 131399379 | |
dc.identifier | 3797b1ab-4d08-4480-a3d2-aaf344670f32 | |
dc.identifier | 000319737700068 | |
dc.identifier | 84877326407 | |
dc.identifier.citation | Childs , K S , Randall , R E & Goodbourn , S 2013 , ' LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA ' , PLoS One , vol. 8 , no. 5 , e64202 . https://doi.org/10.1371/journal.pone.0064202 | en |
dc.identifier.issn | 1932-6203 | |
dc.identifier.other | ORCID: /0000-0002-9304-6678/work/60427018 | |
dc.identifier.uri | https://hdl.handle.net/10023/5028 | |
dc.description | This work was supported by The Wellcome Trust (Grant Numbers AL087751/B to SG and 087751/A/08/Z to RER). (http://www.wellcome.ac.uk/). | en |
dc.description.abstract | The DExD/H box RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene-5 (mda-5) sense viral RNA in the cytoplasm of infected cells and activate signal transduction pathways that trigger the production of type I interferons (IFNs). Laboratory of genetics and physiology 2 (LGP2) is thought to influence IFN production by regulating the activity of RIG-I and mda-5, although its mechanism of action is not known and its function is controversial. Here we show that expression of LGP2 potentiates IFN induction by polyinosinic-polycytidylic acid [poly(I:C)], commonly used as a synthetic mimic of viral dsRNA, and that this is particularly significant at limited levels of the inducer. The observed enhancement is mediated through co-operation with mda-5, which depends upon LGP2 for maximal activation in response to poly(I:C). This co-operation is dependent upon dsRNA binding by LGP2, and the presence of helicase domain IV, both of which are required for LGP2 to interact with mda-5. In contrast, although RIG-I can also be activated by poly(I:C), LGP2 does not have the ability to enhance IFN induction by RIG-I, and instead acts as an inhibitor of RIG-I-dependent poly(I:C) signaling. Thus the level of LGP2 expression is a critical factor in determining the cellular sensitivity to induction by dsRNA, and this may be important for rapid activation of the IFN response at early times post-infection when the levels of inducer are low. | |
dc.format.extent | 8 | |
dc.format.extent | 1847236 | |
dc.language.iso | eng | |
dc.relation.ispartof | PLoS One | en |
dc.subject | Paramyxovirus v-proteins | en |
dc.subject | Inducible gene-I | en |
dc.subject | Innate immune sensor | en |
dc.subject | Ifn-beta promoter | en |
dc.subject | RIG-I | en |
dc.subject | Antiviral responses | en |
dc.subject | Hilicase LGP2 | en |
dc.subject | Signal-transduction | en |
dc.subject | Interferon-beta | en |
dc.subject | Recognition | en |
dc.subject | QH426 Genetics | en |
dc.subject.lcc | QH426 | en |
dc.title | LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA | en |
dc.type | Journal article | en |
dc.contributor.sponsor | The Wellcome Trust | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | 10.1371/journal.pone.0064202 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | 087751/A/08/Z | en |
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