Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex.
The innate immune response plays a key role in fighting infection by activating inflammation and stimulating the adaptive immune response. However, chronic activation of innate immunity can contribute to the pathogenesis of many diseases with an inflammatory component. Thus, various negatively actin...
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doaj-b393c9061e0c477c90d520e3d77d4df82020-11-25T01:23:33ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-02-01112e100493210.1371/journal.pgen.1004932Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex.Brian P O'ConnorThomas DanhornLesly De ArrasBrenna R FlatleyRoland A MarcusEveline Farias-HessonSonia M LeachScott AlperThe innate immune response plays a key role in fighting infection by activating inflammation and stimulating the adaptive immune response. However, chronic activation of innate immunity can contribute to the pathogenesis of many diseases with an inflammatory component. Thus, various negatively acting factors turn off innate immunity subsequent to its activation to ensure that inflammation is self-limiting and to prevent inflammatory disease. These negatively acting pathways include the production of inhibitory acting alternate proteins encoded by alternative mRNA splice forms of genes in Toll-like receptor (TLR) signaling pathways. We previously found that the SF3a mRNA splicing complex was required for a robust innate immune response; SF3a acts to promote inflammation in part by inhibiting the production of a negatively acting splice form of the TLR signaling adaptor MyD88. Here we inhibit SF3a1 using RNAi and subsequently perform an RNAseq study to identify the full complement of genes and splicing events regulated by SF3a in murine macrophages. Surprisingly, in macrophages, SF3a has significant preference for mRNA splicing events within innate immune signaling pathways compared with other biological pathways, thereby affecting the splicing of specific genes in the TLR signaling pathway to modulate the innate immune response.http://europepmc.org/articles/PMC4450051?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Brian P O'Connor Thomas Danhorn Lesly De Arras Brenna R Flatley Roland A Marcus Eveline Farias-Hesson Sonia M Leach Scott Alper |
spellingShingle |
Brian P O'Connor Thomas Danhorn Lesly De Arras Brenna R Flatley Roland A Marcus Eveline Farias-Hesson Sonia M Leach Scott Alper Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex. PLoS Genetics |
author_facet |
Brian P O'Connor Thomas Danhorn Lesly De Arras Brenna R Flatley Roland A Marcus Eveline Farias-Hesson Sonia M Leach Scott Alper |
author_sort |
Brian P O'Connor |
title |
Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex. |
title_short |
Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex. |
title_full |
Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex. |
title_fullStr |
Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex. |
title_full_unstemmed |
Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex. |
title_sort |
regulation of toll-like receptor signaling by the sf3a mrna splicing complex. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2015-02-01 |
description |
The innate immune response plays a key role in fighting infection by activating inflammation and stimulating the adaptive immune response. However, chronic activation of innate immunity can contribute to the pathogenesis of many diseases with an inflammatory component. Thus, various negatively acting factors turn off innate immunity subsequent to its activation to ensure that inflammation is self-limiting and to prevent inflammatory disease. These negatively acting pathways include the production of inhibitory acting alternate proteins encoded by alternative mRNA splice forms of genes in Toll-like receptor (TLR) signaling pathways. We previously found that the SF3a mRNA splicing complex was required for a robust innate immune response; SF3a acts to promote inflammation in part by inhibiting the production of a negatively acting splice form of the TLR signaling adaptor MyD88. Here we inhibit SF3a1 using RNAi and subsequently perform an RNAseq study to identify the full complement of genes and splicing events regulated by SF3a in murine macrophages. Surprisingly, in macrophages, SF3a has significant preference for mRNA splicing events within innate immune signaling pathways compared with other biological pathways, thereby affecting the splicing of specific genes in the TLR signaling pathway to modulate the innate immune response. |
url |
http://europepmc.org/articles/PMC4450051?pdf=render |
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