scholarly journals The splicing factor hnRNP M is a critical regulator of innate immune gene expression in macrophages

2019 ◽  
Author(s):  
K.O. West ◽  
H.M. Scott ◽  
S. Torres-Odio ◽  
A.P. West ◽  
K.L. Patrick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Housekeeping Genes ◽  
Mrna Splicing ◽  
Innate Immune ◽  
Splicing Factor ◽  
Immune Gene ◽  
Control Mechanisms ◽  
Immune Gene Expression ◽  
Innate Immune Gene

ABSTRACTWhile transcriptional control mechanisms of innate immune gene expression are well characterized, almost nothing is known about how pre-mRNA splicing decisions influence, or are influenced by, macrophage activation. Here, we demonstrate that the splicing factor hnRNP M is a critical repressor of innate immune gene expression and that its function is regulated by pathogen sensing cascades. Loss of hnRNP M leads to hyperinduction of a unique regulon of inflammatory and antimicrobial genes, including IL6, Mx1, and Gbp5, following a variety of innate immune stimuli. While mutating specific serines on hnRNP M had little effect on its ability to control pre-mRNA splicing or transcript levels of “housekeeping” genes in resting macrophages, it greatly impacted the protein’s ability to dampen induction of specific innate immune transcripts following activation of pathogen sensing cascades. These data reveal a previously unappreciated role for pattern recognition receptor signaling in controlling splicing factor phosphorylation and establish pre-mRNA splicing as a critical regulatory node in defining innate immune outcomes.

scholarly journals The Splicing Factor hnRNP M Is a Critical Regulator of Innate Immune Gene Expression in Macrophages

Cell Reports ◽  
2019 ◽  
Vol 29 (6) ◽  
pp. 1594-1609.e5 ◽  
Author(s):  
Kelsi O. West ◽  
Haley M. Scott ◽  
Sylvia Torres-Odio ◽  
A. Phillip West ◽  
Kristin L. Patrick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immune ◽  
Splicing Factor ◽  
Immune Gene ◽  
Immune Gene Expression ◽  
Innate Immune Gene

scholarly journals Global Transcriptomics Uncovers Distinct Contributions From Splicing Regulatory Proteins to the Macrophage Innate Immune Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Allison R. Wagner ◽  
Haley M. Scott ◽  
Kelsi O. West ◽  
Krystal J. Vail ◽  
Timothy C. Fitzsimons ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Ex Vivo ◽  
Bacterial Pathogen ◽  
Mrna Splicing ◽  
Innate Immune ◽  
Immune Gene ◽  
Hnrnp K ◽  
Immune Gene Expression ◽  
Innate Immune Gene

Pathogen sensing via pattern recognition receptors triggers massive reprogramming of macrophage gene expression. While the signaling cascades and transcription factors that activate these responses are well-known, the role of post-transcriptional RNA processing in modulating innate immune gene expression remains understudied. Given their crucial role in regulating pre-mRNA splicing and other RNA processing steps, we hypothesized that members of the SR/hnRNP protein families regulate innate immune gene expression in distinct ways. We analyzed steady state gene expression and alternatively spliced isoform production in ten SR/hnRNP knockdown RAW 264.7 macrophage-like cell lines following infection with the bacterial pathogen Salmonella enterica serovar Typhimurium (Salmonella). We identified thousands of transcripts whose abundance is increased or decreased by SR/hnRNP knockdown in macrophages. Notably, we observed that SR and hnRNP proteins influence expression of different genes in uninfected versus Salmonella-infected macrophages, suggesting functionalization of these proteins upon pathogen sensing. Likewise, we found that knockdown of SR/hnRNPs promoted differential isoform usage (DIU) for thousands of macrophage transcripts and that these alternative splicing changes were distinct in uninfected and Salmonella-infected macrophages. Finally, having observed a surprising degree of similarity between the differentially expressed genes (DEGs) and DIUs in hnRNP K and U knockdown macrophages, we found that hnRNP K and U knockdown macrophages are both more restrictive to Vesicular Stomatitis Virus (VSV), while hnRNP K knockdown macrophages are more permissive to Salmonella Typhimurium. Based on these findings, we conclude that many innate immune genes evolved to rely on one or more SR/hnRNPs to ensure the proper magnitude of their induction, supporting a model wherein pre-mRNA splicing is critical for regulating innate immune gene expression and controlling infection outcomes in macrophages ex vivo.

scholarly journals Comparative innate immune gene expression in chicken intestine after in vivo challenge with commensal (Campylobacter) and pathogenic (Salmonella) bacteria

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Ronan Gerard Shaughnessy ◽  
Kieran G. Meade ◽  
Sarah Cahalane ◽  
Brenda Allan ◽  
Carla Reiman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immune ◽  
Immune Gene ◽  
Chicken Intestine ◽  
Immune Gene Expression ◽  
Innate Immune Gene

Innate immune gene expression in individual zebrafish after Listonella anguillarum inoculation

2007 ◽  
Vol 23 (6) ◽  
pp. 1285-1293 ◽  
Author(s):  
Irune Rojo ◽  
Óskar Martínez de Ilárduya ◽  
Andone Estonba ◽  
Miguel Ángel Pardo
Keyword(s):  
Gene Expression ◽  
Innate Immune ◽  
Immune Gene ◽  
Immune Gene Expression ◽  
Listonella Anguillarum ◽  
Innate Immune Gene

scholarly journals Gold nanoparticles exposure modulates antioxidant and innate immune gene expression in the gills of Sparus aurata

Genomics ◽  
2018 ◽  
Vol 110 (6) ◽  
pp. 430-434 ◽  
Author(s):  
Pinanong Na-Phatthalung ◽  
Mariana Teles ◽  
Lluís Tort ◽  
Miguel Oliveira
Keyword(s):  
Gene Expression ◽  
Gold Nanoparticles ◽  
Sparus Aurata ◽  
Innate Immune ◽  
Immune Gene ◽  
Immune Gene Expression ◽  
Innate Immune Gene
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