RNF145 promotes inflammation in recurrent spontaneous abortion through inducing the K63-linked polyubiquitination of IRF3.

Recurrent spontaneous abortion (RSA) is associated with the dysregulation of type Ⅰ interferon (IFN-I) and inflammatory responses. Here, we revealed that IFN-Is and inflammation were upregulated in villus tissues from RSA patients, accompanied by elevated ring finger protein 145 (RNF145) levels and interferon regulatory factor 3 (IRF3) phosphorylation. Moreover, ectopic expression of RNF145 in human embryonic kidney 293 T cells augments IRF3-mediated signalling, leading to the production of IFN-Is and inflammatory cytokines. Mechanistically, RNF145 interacts with IRF3 and induces K63-linked polyubiquitination. Collectively, these findings indicate that RNF145 promotes IFN-I and inflammatory responses in RSA by enhancing IRF3-dependent signalling, highlighting its potential as a biomarker for risk prediction and a therapeutic target for RSA.