Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling
While inflammation induced by Toll-like receptor (TLR) signaling is required to combat infection, persistent inflammation can damage host tissues and contribute to a myriad of acute and chronic inflammatory disorders. Thus, it is essential not only that TLR signaling be activated in the presence of...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1023567/full |
| _version_ | 1798013987222192128 |
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| author | Frank Fang Yao Lee Frank Fang Yao Lee Scott Alper Scott Alper |
| author_facet | Frank Fang Yao Lee Frank Fang Yao Lee Scott Alper Scott Alper |
| author_sort | Frank Fang Yao Lee |
| collection | DOAJ |
| description | While inflammation induced by Toll-like receptor (TLR) signaling is required to combat infection, persistent inflammation can damage host tissues and contribute to a myriad of acute and chronic inflammatory disorders. Thus, it is essential not only that TLR signaling be activated in the presence of pathogens but that TLR signaling is ultimately terminated. One mechanism that limits persistent TLR signaling is alternative pre-mRNA splicing. In addition to encoding the canonical mRNAs that produce proteins that promote inflammation, many genes in the TLR signaling pathway also encode alternative mRNAs that produce proteins that are dominant negative inhibitors of signaling. Many of these negative regulators are induced by immune challenge, so production of these alternative isoforms represents a negative feedback loop that limits persistent inflammation. While these alternative splicing events have been investigated on a gene by gene basis, there has been limited systemic analysis of this mechanism that terminates TLR signaling. Here we review what is known about the production of negatively acting alternative isoforms in the TLR signaling pathway including how these inhibitors function, how they are produced, and what role they may play in inflammatory disease. |
| first_indexed | 2024-04-11T15:11:25Z |
| format | Article |
| id | doaj.art-21e6cd3025054385ad1e5ae3613c5c1a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T15:11:25Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-21e6cd3025054385ad1e5ae3613c5c1a2022-12-22T04:16:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10235671023567Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signalingFrank Fang Yao Lee0Frank Fang Yao Lee1Scott Alper2Scott Alper3Department of Immunology and Genomic Medicine and Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, United StatesDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz, CO, United StatesDepartment of Immunology and Genomic Medicine and Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, United StatesDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz, CO, United StatesWhile inflammation induced by Toll-like receptor (TLR) signaling is required to combat infection, persistent inflammation can damage host tissues and contribute to a myriad of acute and chronic inflammatory disorders. Thus, it is essential not only that TLR signaling be activated in the presence of pathogens but that TLR signaling is ultimately terminated. One mechanism that limits persistent TLR signaling is alternative pre-mRNA splicing. In addition to encoding the canonical mRNAs that produce proteins that promote inflammation, many genes in the TLR signaling pathway also encode alternative mRNAs that produce proteins that are dominant negative inhibitors of signaling. Many of these negative regulators are induced by immune challenge, so production of these alternative isoforms represents a negative feedback loop that limits persistent inflammation. While these alternative splicing events have been investigated on a gene by gene basis, there has been limited systemic analysis of this mechanism that terminates TLR signaling. Here we review what is known about the production of negatively acting alternative isoforms in the TLR signaling pathway including how these inhibitors function, how they are produced, and what role they may play in inflammatory disease.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1023567/fullTLR signalinginnate immunityinflammationpre-mRNA splicingspliceosomeRNA binding protein |
| spellingShingle | Frank Fang Yao Lee Frank Fang Yao Lee Scott Alper Scott Alper Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling Frontiers in Immunology TLR signaling innate immunity inflammation pre-mRNA splicing spliceosome RNA binding protein |
| title | Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling |
| title_full | Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling |
| title_fullStr | Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling |
| title_full_unstemmed | Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling |
| title_short | Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling |
| title_sort | alternative pre mrna splicing as a mechanism for terminating toll like receptor signaling |
| topic | TLR signaling innate immunity inflammation pre-mRNA splicing spliceosome RNA binding protein |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1023567/full |
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