Post-transcriptional regulation of the NLRP3 inflammasome

The NLRP3 inflammasome has taken centre stage as a driver of many common inflammatory conditions, including atherosclerosis and Type 2 diabetes. NLRP3 can be activated, mainly in myeloid cells, by a range of structurally diverse stimuli and drives inflammation by processing the pro-inflammatory cytokines IL-1b and IL-18 and by triggering pyroptosis, a pro-inflammatory type of cell death. Due to its central role in the innate immune system, expression and activation of NLRP3 is tightly regulated, for example transcriptionally by NFκB and by post-translational modifications. Our aim was to test whether NLRP3 expression is also regulated at the post-transcriptional level. We initially identified miR-223 as a negative regulator of NLRP3 expression. More recently, we have identified RNA-binding proteins that can target the NLRP3 3’UTR and an interesting role for alternative polyadenylation in modulating post-transcriptional regulation. Ultimately, better knowledge of NLRP3 regulation could provide insights into differential inflammasome activity between cell types and the pathology of inflammatory diseases.

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Dr Martin Turner
The Brian Heap Seminar Room