Functional specialization of the small interfering RNA pathway in response to virus infection.

In Drosophila, post-transcriptional gene silencing occurs when exogenous or endogenous double stranded RNA (dsRNA) is processed into small interfering RNAs (siRNAs) by Dicer-2 (Dcr-2) in association with a dsRNA-binding protein (dsRBP) cofactor called Loquacious (Loqs-PD). siRNAs are then loaded ont...

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Autores principales:	Joao Trindade Marques, Ji-Ping Wang, Xiaohong Wang, Karla Pollyanna Vieira de Oliveira, Catherine Gao, Eric Roberto Guimaraes Rocha Aguiar, Nadereh Jafari, Richard W Carthew
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/02dcde7e098749f5a519e21fab07a8d4
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spelling	oai:doaj.org-article:02dcde7e098749f5a519e21fab07a8d42021-11-18T06:07:43ZFunctional specialization of the small interfering RNA pathway in response to virus infection.1553-73661553-737410.1371/journal.ppat.1003579https://doaj.org/article/02dcde7e098749f5a519e21fab07a8d42013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24009507/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374In Drosophila, post-transcriptional gene silencing occurs when exogenous or endogenous double stranded RNA (dsRNA) is processed into small interfering RNAs (siRNAs) by Dicer-2 (Dcr-2) in association with a dsRNA-binding protein (dsRBP) cofactor called Loquacious (Loqs-PD). siRNAs are then loaded onto Argonaute-2 (Ago2) by the action of Dcr-2 with another dsRBP cofactor called R2D2. Loaded Ago2 executes the destruction of target RNAs that have sequence complementarity to siRNAs. Although Dcr-2, R2D2, and Ago2 are essential for innate antiviral defense, the mechanism of virus-derived siRNA (vsiRNA) biogenesis and viral target inhibition remains unclear. Here, we characterize the response mechanism mediated by siRNAs against two different RNA viruses that infect Drosophila. In both cases, we show that vsiRNAs are generated by Dcr-2 processing of dsRNA formed during viral genome replication and, to a lesser extent, viral transcription. These vsiRNAs seem to preferentially target viral polyadenylated RNA to inhibit viral replication. Loqs-PD is completely dispensable for silencing of the viruses, in contrast to its role in silencing endogenous targets. Biogenesis of vsiRNAs is independent of both Loqs-PD and R2D2. R2D2, however, is required for sorting and loading of vsiRNAs onto Ago2 and inhibition of viral RNA expression. Direct injection of viral RNA into Drosophila results in replication that is also independent of Loqs-PD. This suggests that triggering of the antiviral pathway is not related to viral mode of entry but recognition of intrinsic features of virus RNA. Our results indicate the existence of a vsiRNA pathway that is separate from the endogenous siRNA pathway and is specifically triggered by virus RNA. We speculate that this unique framework might be necessary for a prompt and efficient antiviral response.Joao Trindade MarquesJi-Ping WangXiaohong WangKarla Pollyanna Vieira de OliveiraCatherine GaoEric Roberto Guimaraes Rocha AguiarNadereh JafariRichard W CarthewPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 8, p e1003579 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Joao Trindade Marques Ji-Ping Wang Xiaohong Wang Karla Pollyanna Vieira de Oliveira Catherine Gao Eric Roberto Guimaraes Rocha Aguiar Nadereh Jafari Richard W Carthew Functional specialization of the small interfering RNA pathway in response to virus infection.
description	In Drosophila, post-transcriptional gene silencing occurs when exogenous or endogenous double stranded RNA (dsRNA) is processed into small interfering RNAs (siRNAs) by Dicer-2 (Dcr-2) in association with a dsRNA-binding protein (dsRBP) cofactor called Loquacious (Loqs-PD). siRNAs are then loaded onto Argonaute-2 (Ago2) by the action of Dcr-2 with another dsRBP cofactor called R2D2. Loaded Ago2 executes the destruction of target RNAs that have sequence complementarity to siRNAs. Although Dcr-2, R2D2, and Ago2 are essential for innate antiviral defense, the mechanism of virus-derived siRNA (vsiRNA) biogenesis and viral target inhibition remains unclear. Here, we characterize the response mechanism mediated by siRNAs against two different RNA viruses that infect Drosophila. In both cases, we show that vsiRNAs are generated by Dcr-2 processing of dsRNA formed during viral genome replication and, to a lesser extent, viral transcription. These vsiRNAs seem to preferentially target viral polyadenylated RNA to inhibit viral replication. Loqs-PD is completely dispensable for silencing of the viruses, in contrast to its role in silencing endogenous targets. Biogenesis of vsiRNAs is independent of both Loqs-PD and R2D2. R2D2, however, is required for sorting and loading of vsiRNAs onto Ago2 and inhibition of viral RNA expression. Direct injection of viral RNA into Drosophila results in replication that is also independent of Loqs-PD. This suggests that triggering of the antiviral pathway is not related to viral mode of entry but recognition of intrinsic features of virus RNA. Our results indicate the existence of a vsiRNA pathway that is separate from the endogenous siRNA pathway and is specifically triggered by virus RNA. We speculate that this unique framework might be necessary for a prompt and efficient antiviral response.
format	article
author	Joao Trindade Marques Ji-Ping Wang Xiaohong Wang Karla Pollyanna Vieira de Oliveira Catherine Gao Eric Roberto Guimaraes Rocha Aguiar Nadereh Jafari Richard W Carthew
author_facet	Joao Trindade Marques Ji-Ping Wang Xiaohong Wang Karla Pollyanna Vieira de Oliveira Catherine Gao Eric Roberto Guimaraes Rocha Aguiar Nadereh Jafari Richard W Carthew
author_sort	Joao Trindade Marques
title	Functional specialization of the small interfering RNA pathway in response to virus infection.
title_short	Functional specialization of the small interfering RNA pathway in response to virus infection.
title_full	Functional specialization of the small interfering RNA pathway in response to virus infection.
title_fullStr	Functional specialization of the small interfering RNA pathway in response to virus infection.
title_full_unstemmed	Functional specialization of the small interfering RNA pathway in response to virus infection.
title_sort	functional specialization of the small interfering rna pathway in response to virus infection.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/02dcde7e098749f5a519e21fab07a8d4
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Functional specialization of the small interfering RNA pathway in response to virus infection.

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