Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription
Summary: Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA-binding proteins (RBPs) to shaping the macrophage response to pathogens remains poorly understood. Transcriptomic analysis reveals that a member...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472400144X |
| _version_ | 1797296228657004544 |
|---|---|
| author | Haley M. Scott Mackenzie H. Smith Aja K. Coleman Kaitlyn S. Armijo Morgan J. Chapman Summer L. Apostalo Allison R. Wagner Robert O. Watson Kristin L. Patrick |
| author_facet | Haley M. Scott Mackenzie H. Smith Aja K. Coleman Kaitlyn S. Armijo Morgan J. Chapman Summer L. Apostalo Allison R. Wagner Robert O. Watson Kristin L. Patrick |
| author_sort | Haley M. Scott |
| collection | DOAJ |
| description | Summary: Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA-binding proteins (RBPs) to shaping the macrophage response to pathogens remains poorly understood. Transcriptomic analysis reveals that a member of the serine/arginine-rich (SR) family of mRNA processing factors, SRSF7, is required for optimal expression of a cohort of interferon-stimulated genes in macrophages. Using genetic and biochemical assays, we discover that in addition to its canonical role in regulating alternative splicing, SRSF7 drives transcription of interferon regulatory transcription factor 7 (IRF7) to promote antiviral immunity. At the Irf7 promoter, SRSF7 maximizes STAT1 transcription factor binding and RNA polymerase II elongation via cooperation with the H4K20me1 histone methyltransferase KMT5a (SET8). These studies define a role for an SR protein in activating transcription and reveal an RBP-chromatin network that orchestrates macrophage antiviral gene expression. |
| first_indexed | 2024-03-07T22:01:25Z |
| format | Article |
| id | doaj.art-b8e107d3d69e4d6bae0a464021f10cb9 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-07T22:01:25Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b8e107d3d69e4d6bae0a464021f10cb92024-02-24T04:54:47ZengElsevierCell Reports2211-12472024-03-01433113816Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcriptionHaley M. Scott0Mackenzie H. Smith1Aja K. Coleman2Kaitlyn S. Armijo3Morgan J. Chapman4Summer L. Apostalo5Allison R. Wagner6Robert O. Watson7Kristin L. Patrick8Department of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine, Bryan, TX 77807, USA; Corresponding authorSummary: Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA-binding proteins (RBPs) to shaping the macrophage response to pathogens remains poorly understood. Transcriptomic analysis reveals that a member of the serine/arginine-rich (SR) family of mRNA processing factors, SRSF7, is required for optimal expression of a cohort of interferon-stimulated genes in macrophages. Using genetic and biochemical assays, we discover that in addition to its canonical role in regulating alternative splicing, SRSF7 drives transcription of interferon regulatory transcription factor 7 (IRF7) to promote antiviral immunity. At the Irf7 promoter, SRSF7 maximizes STAT1 transcription factor binding and RNA polymerase II elongation via cooperation with the H4K20me1 histone methyltransferase KMT5a (SET8). These studies define a role for an SR protein in activating transcription and reveal an RBP-chromatin network that orchestrates macrophage antiviral gene expression.http://www.sciencedirect.com/science/article/pii/S221112472400144XCP: Molecular biologyCP: Cell biology |
| spellingShingle | Haley M. Scott Mackenzie H. Smith Aja K. Coleman Kaitlyn S. Armijo Morgan J. Chapman Summer L. Apostalo Allison R. Wagner Robert O. Watson Kristin L. Patrick Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription Cell Reports CP: Molecular biology CP: Cell biology |
| title | Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription |
| title_full | Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription |
| title_fullStr | Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription |
| title_full_unstemmed | Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription |
| title_short | Serine/arginine-rich splicing factor 7 promotes the type I interferon response by activating Irf7 transcription |
| title_sort | serine arginine rich splicing factor 7 promotes the type i interferon response by activating irf7 transcription |
| topic | CP: Molecular biology CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S221112472400144X |
| work_keys_str_mv | AT haleymscott serineargininerichsplicingfactor7promotesthetypeiinterferonresponsebyactivatingirf7transcription AT mackenziehsmith serineargininerichsplicingfactor7promotesthetypeiinterferonresponsebyactivatingirf7transcription AT ajakcoleman serineargininerichsplicingfactor7promotesthetypeiinterferonresponsebyactivatingirf7transcription AT kaitlynsarmijo serineargininerichsplicingfactor7promotesthetypeiinterferonresponsebyactivatingirf7transcription AT morganjchapman serineargininerichsplicingfactor7promotesthetypeiinterferonresponsebyactivatingirf7transcription AT summerlapostalo serineargininerichsplicingfactor7promotesthetypeiinterferonresponsebyactivatingirf7transcription AT allisonrwagner serineargininerichsplicingfactor7promotesthetypeiinterferonresponsebyactivatingirf7transcription AT robertowatson serineargininerichsplicingfactor7promotesthetypeiinterferonresponsebyactivatingirf7transcription AT kristinlpatrick serineargininerichsplicingfactor7promotesthetypeiinterferonresponsebyactivatingirf7transcription |