Cargando…
DUSP11-mediated control of 5′-triphosphate RNA regulates RIG-I sensitivity
Deciphering the mechanisms that regulate the sensitivity of pathogen recognition receptors is imperative to understanding infection and inflammation. Here we demonstrate that the RNA triphosphatase dual-specificity phosphatase 11 (DUSP11) acts on both host and virus-derived 5′-triphosphate RNAs rend...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706711/ https://www.ncbi.nlm.nih.gov/pubmed/33184222 http://dx.doi.org/10.1101/gad.340604.120 |
_version_ | 1783617206447243264 |
---|---|
author | Choi, Joon H. Burke, James M. Szymanik, Kayla H. Nepal, Upasana Battenhouse, Anna Lau, Justin T. Stark, Aaron Lam, Victor Sullivan, Christopher S. |
author_facet | Choi, Joon H. Burke, James M. Szymanik, Kayla H. Nepal, Upasana Battenhouse, Anna Lau, Justin T. Stark, Aaron Lam, Victor Sullivan, Christopher S. |
author_sort | Choi, Joon H. |
collection | PubMed |
description | Deciphering the mechanisms that regulate the sensitivity of pathogen recognition receptors is imperative to understanding infection and inflammation. Here we demonstrate that the RNA triphosphatase dual-specificity phosphatase 11 (DUSP11) acts on both host and virus-derived 5′-triphosphate RNAs rendering them less active in inducing a RIG-I-mediated immune response. Reducing DUSP11 levels alters host triphosphate RNA packaged in extracellular vesicles and induces enhanced RIG-I activation in cells exposed to extracellular vesicles. Virus infection of cells lacking DUSP11 results in a higher proportion of triphosphorylated viral transcripts and attenuated virus replication, which is rescued by reducing RIG-I expression. Consistent with the activity of DUSP11 in the cellular RIG-I response, mice lacking DUSP11 display lower viral loads, greater sensitivity to triphosphorylated RNA, and a signature of enhanced interferon activity in select tissues. Our results reveal the importance of controlling 5′-triphosphate RNA levels to prevent aberrant RIG-I signaling and demonstrate DUSP11 as a key effector of this mechanism. |
format | Online Article Text |
id | pubmed-7706711 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77067112020-12-09 DUSP11-mediated control of 5′-triphosphate RNA regulates RIG-I sensitivity Choi, Joon H. Burke, James M. Szymanik, Kayla H. Nepal, Upasana Battenhouse, Anna Lau, Justin T. Stark, Aaron Lam, Victor Sullivan, Christopher S. Genes Dev Research Paper Deciphering the mechanisms that regulate the sensitivity of pathogen recognition receptors is imperative to understanding infection and inflammation. Here we demonstrate that the RNA triphosphatase dual-specificity phosphatase 11 (DUSP11) acts on both host and virus-derived 5′-triphosphate RNAs rendering them less active in inducing a RIG-I-mediated immune response. Reducing DUSP11 levels alters host triphosphate RNA packaged in extracellular vesicles and induces enhanced RIG-I activation in cells exposed to extracellular vesicles. Virus infection of cells lacking DUSP11 results in a higher proportion of triphosphorylated viral transcripts and attenuated virus replication, which is rescued by reducing RIG-I expression. Consistent with the activity of DUSP11 in the cellular RIG-I response, mice lacking DUSP11 display lower viral loads, greater sensitivity to triphosphorylated RNA, and a signature of enhanced interferon activity in select tissues. Our results reveal the importance of controlling 5′-triphosphate RNA levels to prevent aberrant RIG-I signaling and demonstrate DUSP11 as a key effector of this mechanism. Cold Spring Harbor Laboratory Press 2020-12-01 /pmc/articles/PMC7706711/ /pubmed/33184222 http://dx.doi.org/10.1101/gad.340604.120 Text en © 2020 Choi et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Paper Choi, Joon H. Burke, James M. Szymanik, Kayla H. Nepal, Upasana Battenhouse, Anna Lau, Justin T. Stark, Aaron Lam, Victor Sullivan, Christopher S. DUSP11-mediated control of 5′-triphosphate RNA regulates RIG-I sensitivity |
title | DUSP11-mediated control of 5′-triphosphate RNA regulates RIG-I sensitivity |
title_full | DUSP11-mediated control of 5′-triphosphate RNA regulates RIG-I sensitivity |
title_fullStr | DUSP11-mediated control of 5′-triphosphate RNA regulates RIG-I sensitivity |
title_full_unstemmed | DUSP11-mediated control of 5′-triphosphate RNA regulates RIG-I sensitivity |
title_short | DUSP11-mediated control of 5′-triphosphate RNA regulates RIG-I sensitivity |
title_sort | dusp11-mediated control of 5′-triphosphate rna regulates rig-i sensitivity |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706711/ https://www.ncbi.nlm.nih.gov/pubmed/33184222 http://dx.doi.org/10.1101/gad.340604.120 |
work_keys_str_mv | AT choijoonh dusp11mediatedcontrolof5triphosphaternaregulatesrigisensitivity AT burkejamesm dusp11mediatedcontrolof5triphosphaternaregulatesrigisensitivity AT szymanikkaylah dusp11mediatedcontrolof5triphosphaternaregulatesrigisensitivity AT nepalupasana dusp11mediatedcontrolof5triphosphaternaregulatesrigisensitivity AT battenhouseanna dusp11mediatedcontrolof5triphosphaternaregulatesrigisensitivity AT laujustint dusp11mediatedcontrolof5triphosphaternaregulatesrigisensitivity AT starkaaron dusp11mediatedcontrolof5triphosphaternaregulatesrigisensitivity AT lamvictor dusp11mediatedcontrolof5triphosphaternaregulatesrigisensitivity AT sullivanchristophers dusp11mediatedcontrolof5triphosphaternaregulatesrigisensitivity |