RNF126 Promotes Endoplasmic Reticulum Stress in Fetal Growth Restriction via Ubiquitination-Mediated Degradation of the MYH9/MYH10 Complex

Fetal growth restriction (FGR) stands as a prominent cause of neonatal morbidity and mortality, yet its underlying mechanisms remain elusive. Through a multi-omics analysis of the human placentas, including quantitative proteomics and ubiquitination-modified proteomics, our team find that the E3 ligase Ring finger protein 126 (RNF126) might be a potentially pivotal protein in the development of FGR. Here, we have discovered that RNF126 can induce endoplasmic reticulum stress (ERS) in placental trophoblasts through RNA sequencing, leading to an increase in apoptosis rates. Subsequent studies have confirmed that RNF126 promotes the degradation of the MYH9/MYH10 complex via the ubiquitin-proteasome pathway, thereby contributing to ERS and inducing trophoblast dysfunction. Meanwhile, Our RNF126 placenta-specific knockout mouse model (cKO) validates these findings in vivo. These events significantly contribute to the occurrence and progression of FGR. This study provides new insights and highlights the promising potential of RNF126 as a therapeutic target for FGR treatment. We conducted RNA-seq on BeWo cells that were stably overexpressed with empty vector (OE-NC) or RNF126 (OE-RNF126) using lentiviruses. n = 3 biologically independent experiments.