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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
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.
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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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