Eicke Latz Laboratory

NLR splicing

Post-transcriptional regulation of NLRs creates diversity

Project details

What is the function of differential utilization of LRRs modules in vertebrate innate immunity?

Leucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. We found a strict exonic modularity of LRR domains of several human gene families, which is a precondition for alternative splicing (AS). We found that the LRR domain within several Nod-like receptors, including the inflammasome sensor NLRP3, undergoes elaborate modular splicing events.

We identified that NLRP3 alternative splicing is stochastically regulated, with NLRP3 Δ exon 5 lacking the interaction surface for NEK7 and hence loss of activity.

In this project we aim to understand how alternative splicing within NLR LRRs is regulated and how alternative splicing of NLRs can influence their function and ligand repertoire.

Project-related publications

Alternative splicing regulates stochastic NLRP3 activity

Hoss F, Mueller JL, Rojas Ringeling F, Rodriguez-Alcazar JF, Brinkschulte R, Seifert G, Stahl R, Broderick L, Putnam CD, Kolodner RD, Canzar S, Geyer M, Hoffman HM, Latz E.

Nat Commun. 2019 Jul 19;10(1):3238. doi: 10.1038/s41467-019-11076-1.

Project-related funding

ERC Consolidator grant

European Research Council

Project-related scientists

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