Journal
PLOS ONE
Volume 6, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0019829
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Funding
- Fundacao Luso-Americana para o Desenvolvimento
- Fundacao para a Ciencia e a Tecnologia [PTDC/SAU-MII/100780/2008, PIC/IC/82991/2007]
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-MII/100780/2008, PIC/IC/82991/2007] Funding Source: FCT
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The generation of diversity and plasticity of transcriptional programs are key components of effective vertebrate immune responses. The role of Alternative Splicing has been recognized, but it is underappreciated and poorly understood as a critical mechanism for the regulation and fine-tuning of physiological immune responses. Here we report the generation of loss-of-function phenotypes for a large collection of genes known or predicted to be involved in the splicing reaction and the identification of 19 novel regulators of IL-1 beta secretion in response to E. coli challenge of THP-1 cells. Twelve of these genes are required for IL-1 beta secretion, while seven are negative regulators of this process. Silencing of SFRS3 increased IL-1 beta secretion due to elevation of IL-1 beta and caspase-1 mRNA in addition to active caspase-1 levels. This study points to the relevance of splicing in the regulation of auto-inflammatory diseases.
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