By DoM Communications | Date published: March 13, 2025
Fitzgerald and Lien Labs Identify Splicing Factor as Important Player in Immune Response Regulation
During the past few years, mRNA, the mature form of RNA coding for proteins, has become a commonly known term. A large portion of the population has, by now, received injections of mRNA coding for microbial proteins during vaccinations. During a normal cell process, before mRNA is generated, pre-mRNA is produced, and splicing factors aid in gluing together a mature mRNA from specific parts called exons, laying the foundation for the correct production of proteins. The function in immunity for many of these splicing factors is not known.
Researchers in the Fitzgerald and Lien labs, along with their colleagues, aimed to better understand the regulation of immune responses, and during a screen identified a splicing factor as an important player. In their study published in PNAS, they found that the splicing factor Raver1 is responsible for the generation of normal mRNA for an immune-regulating protein called RIPK1. In the absence of Raver1, immune cell inflammation and cell death induced by Yersinia bacteria and inflammatory cytokines via actions of RIPK1 and the related enzyme caspase-8 were blunted. This was accompanied by the production of an incorrectly spliced, abbreviated, and dysfunctional form of RIPK1.
The biological significance of these findings was emphasized by the fact that mice lacking Raver1 were highly susceptible to infection. Thus, the Raver1 splicing factor safeguards a protective inflammatory and anti-microbial response for the host.