Alternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrix
The identification of barely more than 20,000 human genes was amongst the most surprising outcomes of the human genome project. Alternative splicing provides an essential means of expanding the proteome, enabling a single gene to encode multiple, distinct isoforms by selective inclusion or exclusion...
| Main Authors: | , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2020
|
| _version_ | 1797101440123011072 |
|---|---|
| author | Giblin, SP Schwenzer, A Midwood, KS |
| author_facet | Giblin, SP Schwenzer, A Midwood, KS |
| author_sort | Giblin, SP |
| collection | OXFORD |
| description | The identification of barely more than 20,000 human genes was amongst the most surprising outcomes of the human genome project. Alternative splicing provides an essential means of expanding the proteome, enabling a single gene to encode multiple, distinct isoforms by selective inclusion or exclusion of exons from mature mRNA. However, mis-regulation of this process is associated with most human diseases. Here, we examine the impact of post-transcriptional processing on extracellular matrix function, focusing on the complex alternative splicing patterns of tenascin-C, a molecule that can exist in as many as 500 different isoforms. We demonstrate that the pro-inflammatory activity of this endogenous innate immune trigger is controlled by inclusion or exclusion of a novel immunomodulatory site located within domains AD2AD1, identifying this as a mechanism that prevents unnecessary inflammation in healthy tissues but enables rapid immune cell mobilization and activation upon tissue damage, and defining how this goes awry in autoimmune disease. |
| first_indexed | 2024-03-07T05:51:58Z |
| format | Journal article |
| id | oxford-uuid:e933ec00-97ea-4e0b-9bea-565b536a2a67 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:51:58Z |
| publishDate | 2020 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:e933ec00-97ea-4e0b-9bea-565b536a2a672022-03-27T10:52:33ZAlternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrixJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e933ec00-97ea-4e0b-9bea-565b536a2a67EnglishSymplectic ElementsElsevier2020Giblin, SPSchwenzer, AMidwood, KSThe identification of barely more than 20,000 human genes was amongst the most surprising outcomes of the human genome project. Alternative splicing provides an essential means of expanding the proteome, enabling a single gene to encode multiple, distinct isoforms by selective inclusion or exclusion of exons from mature mRNA. However, mis-regulation of this process is associated with most human diseases. Here, we examine the impact of post-transcriptional processing on extracellular matrix function, focusing on the complex alternative splicing patterns of tenascin-C, a molecule that can exist in as many as 500 different isoforms. We demonstrate that the pro-inflammatory activity of this endogenous innate immune trigger is controlled by inclusion or exclusion of a novel immunomodulatory site located within domains AD2AD1, identifying this as a mechanism that prevents unnecessary inflammation in healthy tissues but enables rapid immune cell mobilization and activation upon tissue damage, and defining how this goes awry in autoimmune disease. |
| spellingShingle | Giblin, SP Schwenzer, A Midwood, KS Alternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrix |
| title | Alternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrix |
| title_full | Alternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrix |
| title_fullStr | Alternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrix |
| title_full_unstemmed | Alternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrix |
| title_short | Alternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrix |
| title_sort | alternative splicing controls cell lineage specific responses to endogenous innate immune triggers within the extracellular matrix |
| work_keys_str_mv | AT giblinsp alternativesplicingcontrolscelllineagespecificresponsestoendogenousinnateimmunetriggerswithintheextracellularmatrix AT schwenzera alternativesplicingcontrolscelllineagespecificresponsestoendogenousinnateimmunetriggerswithintheextracellularmatrix AT midwoodks alternativesplicingcontrolscelllineagespecificresponsestoendogenousinnateimmunetriggerswithintheextracellularmatrix |