Alternative splicing regulates stochastic NLRP3 activity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31324763.
- Also identified by DOI 10.1038/s41467-019-11076-1 and PMC identifier 6642158.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Alternative Splicing
- Exons
- Inflammasomes
- NLR Family, Pyrin Domain-Containing 3 Protein