Department of Medicine, Division of Infectious Diseases and Immunology
Amino Acids, Peptides, and Proteins | Biochemical Phenomena, Metabolism, and Nutrition | Genetic Phenomena | Hemic and Immune Systems | Immunity | Nucleic Acids, Nucleotides, and Nucleosides
Leucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. Here we report strict exonic modularity of LRR domains of several human gene families, which is a precondition for alternative splicing (AS). We provide evidence for AS of LRR domain within several Nod-like receptors, most prominently the inflammasome sensor NLRP3. Human NLRP3, but not mouse NLRP3, is expressed as two major isoforms, the full-length variant and a variant lacking exon 5. Moreover, NLRP3 AS is stochastically regulated, with NLRP3 exon 5 lacking the interaction surface for NEK7 and hence loss of activity. Our data thus reveals unexpected regulatory roles of AS through differential utilization of LRRs modules in vertebrate innate immunity.
Inflammasome, Innate immunity, NOD-like receptors, RNA splicing
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DOI of Published Version
Nat Commun. 2019 Jul 19;10(1):3238. doi: 10.1038/s41467-019-11076-1. Link to article on publisher's site
Hoss, Florian; Mueller, James L.; Rojas Ringeling, Francisca; Rodriguez-Alcazar, Juan F.; Brinkschulte, Rebecca; Seifert, Gerald; Stahl, Rainer; Broderick, Lori; Putnam, Chris D.; Kolodner, Richard D.; Canzar, Stefan; Geyer, Matthias; Hoffman, Hal M.; and Latz, Eicke, "Alternative splicing regulates stochastic NLRP3 activity" (2019). Open Access Articles. 3929.
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