UBL5 Modulates Expression of Crucial TLR Pathway Genes and Inflammasome Activation in Human Macrophage Cells

نویسندگان

چکیده

Abstract We conducted a genome-wide siRNA screen for regulators of LPS-driven TNF expression in macrophages. used splicing-independent reporter the screen, and while we identified very few core spliceosome components among strongest hits, observed clear enrichment peripheral splicing regulators. Among these, novel putative regulator, UBL5, gave strong phenotype, UBL5 shRNA-expressing cell line showed selective defect gene expression. While many genes were induced normally by LPS deficient cells, subset genes, including LPS-activated TLR4 signaling pathway, substantially diminished UBL5-deficient cells. both Illumina Pacbio long-read sequencing, marked defects LPS-induced numerous however primary impact on known pathway was at level overall rather than alternative splicing. Our data suggests that regulator also has key roles maintenance induction several pathway. Key role further evidenced defective NLRP3 inflammasome activation protection OC43 coronavirus infection This work supported Intramural Research Program NIAID, NIH

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ژورنال

عنوان ژورنال: Journal of Immunology

سال: 2023

ISSN: ['1550-6606', '0022-1767']

DOI: https://doi.org/10.4049/jimmunol.210.supp.167.19