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Public Library of Science, PLoS ONE, 5(6), p. e19829, 2011

DOI: 10.1371/journal.pone.0019829

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An shRNA-Based Screen of Splicing Regulators Identifies SFRS3 as a Negative Regulator of IL-1β Secretion

Journal article published in 2011 by Pedro Moura-Alves, Ana Neves-Costa ORCID, Helena Raquel, Teresa Raquel Pacheco, Bruno D'Almeida, Raquel Rodrigues, Iris Cadima-Couto, Ângelo Chora, Mariana Oliveira, Margarida Gama-Carvalho, Nir Hacohen, Luis F. Moita ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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-1β secretion in response to E. coli challenge of THP-1 cells. Twelve of these genes are required for IL-1β secretion, while seven are negative regulators of this process. Silencing of SFRS3 increased IL-1β secretion due to elevation of IL-1β 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.