Raver1 links <i>Ripk1</i> RNA splicing to caspase-8-mediated pyroptotic cell death, inflammation, and pathogen resistance.

ABSTRACT: Multiple cell death and inflammatory signaling pathways converge on two critical factors: receptor-interacting serine/threonine kinase 1 (RIPK1) and caspase-8. Careful regulation of these molecules is critical to control apoptosis, pyroptosis, and inflammation. Here, we found a pivotal role of Raver1 as an essential regulator of Ripk1 pre-mRNA splicing, expression, and functionality and the subsequent caspase-8-dependent inflammatory cell death. We show that Raver1 influences mRNA diversity primarily by repressing alternative exon inclusion. Macrophages from Raver1-deficient mice exhibit altered splicing of Ripk1. As a result, Raver1-deficient primary macrophages display diminished cell death and decreased interleukin-18 and interleukin-1ß production, when infec

SUBMITTER: Zhang B 

PROVIDER: S-EPMC11848402 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature