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IL-17 receptor-associated adaptor Act1 directly stabilizes mRNAs to mediate IL-17 inflammatory signaling
Mechanisms that degrade inflammatory mRNAs are well-known, however stabilizing mechanisms are poorly understood. Here we show that Act1, an interleukin-17 (IL-17) receptor complex adaptor, binds and stabilizes mRNAs encoding key inflammatory proteins. The Act1 SEFIR domain binds a stem-loop structur...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082628/ https://www.ncbi.nlm.nih.gov/pubmed/29563620 http://dx.doi.org/10.1038/s41590-018-0071-9 |
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author | Herjan, Tomasz Hong, Lingzi Bubenik, Jodi Bulek, Katarzyna Qian, Wen Liu, Caini Li, Xiao Chen, Xing Yang, Hui Ouyang, Suidong Zhou, Hao Zhao, Junjie Komireddy, Vasu Cockman, Eric Aronica, Mark Asosingh, Kewal Licatalosi, Donny D. Qin, Jun Fox, Paul L. Hamilton, Thomas A. Driscoll, Donna Li, Xiaoxia |
author_facet | Herjan, Tomasz Hong, Lingzi Bubenik, Jodi Bulek, Katarzyna Qian, Wen Liu, Caini Li, Xiao Chen, Xing Yang, Hui Ouyang, Suidong Zhou, Hao Zhao, Junjie Komireddy, Vasu Cockman, Eric Aronica, Mark Asosingh, Kewal Licatalosi, Donny D. Qin, Jun Fox, Paul L. Hamilton, Thomas A. Driscoll, Donna Li, Xiaoxia |
author_sort | Herjan, Tomasz |
collection | PubMed |
description | Mechanisms that degrade inflammatory mRNAs are well-known, however stabilizing mechanisms are poorly understood. Here we show that Act1, an interleukin-17 (IL-17) receptor complex adaptor, binds and stabilizes mRNAs encoding key inflammatory proteins. The Act1 SEFIR domain binds a stem-loop structure, SBE (SEFIR-binding element), in the inflammatory chemokine Cxcl1 3’ UTR. mRNA-bound Act1 directs formation of three compartmentally-distinct protein-RNA complexes (RNPs) that regulate three disparate events in inflammatory mRNA metabolism: preventing mRNA decay in the nucleus, inhibiting mRNA decapping in P-bodies, and promoting translation. SBE RNA aptamers reduced IL-17-mediated mRNA stabilization in vitro, IL-17-induced skin inflammation and airway inflammation in a mouse asthma model, providing a therapeutic strategy for autoimmune diseases. These results reveal a network in which Act1 assembles RNPs on the 3’ UTRs of select mRNAs to control receptor-mediated mRNA stabilization and translation during inflammation. |
format | Online Article Text |
id | pubmed-6082628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-60826282018-09-21 IL-17 receptor-associated adaptor Act1 directly stabilizes mRNAs to mediate IL-17 inflammatory signaling Herjan, Tomasz Hong, Lingzi Bubenik, Jodi Bulek, Katarzyna Qian, Wen Liu, Caini Li, Xiao Chen, Xing Yang, Hui Ouyang, Suidong Zhou, Hao Zhao, Junjie Komireddy, Vasu Cockman, Eric Aronica, Mark Asosingh, Kewal Licatalosi, Donny D. Qin, Jun Fox, Paul L. Hamilton, Thomas A. Driscoll, Donna Li, Xiaoxia Nat Immunol Article Mechanisms that degrade inflammatory mRNAs are well-known, however stabilizing mechanisms are poorly understood. Here we show that Act1, an interleukin-17 (IL-17) receptor complex adaptor, binds and stabilizes mRNAs encoding key inflammatory proteins. The Act1 SEFIR domain binds a stem-loop structure, SBE (SEFIR-binding element), in the inflammatory chemokine Cxcl1 3’ UTR. mRNA-bound Act1 directs formation of three compartmentally-distinct protein-RNA complexes (RNPs) that regulate three disparate events in inflammatory mRNA metabolism: preventing mRNA decay in the nucleus, inhibiting mRNA decapping in P-bodies, and promoting translation. SBE RNA aptamers reduced IL-17-mediated mRNA stabilization in vitro, IL-17-induced skin inflammation and airway inflammation in a mouse asthma model, providing a therapeutic strategy for autoimmune diseases. These results reveal a network in which Act1 assembles RNPs on the 3’ UTRs of select mRNAs to control receptor-mediated mRNA stabilization and translation during inflammation. 2018-03-21 2018-04 /pmc/articles/PMC6082628/ /pubmed/29563620 http://dx.doi.org/10.1038/s41590-018-0071-9 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Herjan, Tomasz Hong, Lingzi Bubenik, Jodi Bulek, Katarzyna Qian, Wen Liu, Caini Li, Xiao Chen, Xing Yang, Hui Ouyang, Suidong Zhou, Hao Zhao, Junjie Komireddy, Vasu Cockman, Eric Aronica, Mark Asosingh, Kewal Licatalosi, Donny D. Qin, Jun Fox, Paul L. Hamilton, Thomas A. Driscoll, Donna Li, Xiaoxia IL-17 receptor-associated adaptor Act1 directly stabilizes mRNAs to mediate IL-17 inflammatory signaling |
title | IL-17 receptor-associated adaptor Act1 directly stabilizes mRNAs to
mediate IL-17 inflammatory signaling |
title_full | IL-17 receptor-associated adaptor Act1 directly stabilizes mRNAs to
mediate IL-17 inflammatory signaling |
title_fullStr | IL-17 receptor-associated adaptor Act1 directly stabilizes mRNAs to
mediate IL-17 inflammatory signaling |
title_full_unstemmed | IL-17 receptor-associated adaptor Act1 directly stabilizes mRNAs to
mediate IL-17 inflammatory signaling |
title_short | IL-17 receptor-associated adaptor Act1 directly stabilizes mRNAs to
mediate IL-17 inflammatory signaling |
title_sort | il-17 receptor-associated adaptor act1 directly stabilizes mrnas to
mediate il-17 inflammatory signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082628/ https://www.ncbi.nlm.nih.gov/pubmed/29563620 http://dx.doi.org/10.1038/s41590-018-0071-9 |
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