Hoss, FlorianMueller, James L.Rojas Ringeling, FranciscaRodriguez-Alcazar, Juan F.Brinkschulte, RebeccaSeifert, GeraldStahl, RainerBroderick, LoriPutnam, Chris D.Kolodner, Richard D.Canzar, StefanGeyer, MatthiasHoffman, Hal M.Latz, Eicke2022-08-232022-08-232019-07-192019-08-09<p>Nat Commun. 2019 Jul 19;10(1):3238. doi: 10.1038/s41467-019-11076-1. <a href="https://doi.org/10.1038/s41467-019-11076-1">Link to article on publisher's site</a></p>2041-1723 (Linking)10.1038/s41467-019-11076-131324763https://hdl.handle.net/20.500.14038/41139Leucine-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.en-USCopyright © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/InflammasomeInnate immunityNOD-like receptorsRNA splicingAmino Acids, Peptides, and ProteinsBiochemical Phenomena, Metabolism, and NutritionGenetic PhenomenaHemic and Immune SystemsImmunityNucleic Acids, Nucleotides, and NucleosidesJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4945&amp;context=oapubs&amp;unstamped=1https://escholarship.umassmed.edu/oapubs/392915087850oapubs/3929