Circular RNA hsa_circ_0081343 modulates trophoblast autophagy through Rbm8a nuclear translocation

Fetal growth restriction (FGR) is a kind of obstetric complication that seriously endangers fetal life. Recent studies reported significant reduction of hsa_circ_0081343 in human placenta developed in FGR and is involved in cell migration, invasion, and apoptosis of trophoblast by acting as microRNA sponges. Autophagy is required for invasion of trophoblast cells and for vascular remodeling during placentation. In this study, we aimed to explore the mechanistic link between hsa_circ_0081343 and autophagy.

We investigated the interactions between hsa_circ_0081343 and RNA-binding proteins were studied by RNA pull-down assay, mass spectrometry and RNA immunoprecipitation assay. The mechanism of nuclear translocation of Rbm8a were assessed by reverse transcription-quantitative PCR, Western blot, immunofluorescence and Co-Immunoprecipitation. Western blot, immunofluorescence and transmission electron microscopy were performed to elucidate the mechanism underlying hsa_circ_0081343 and/or Rbm8a mediated regulation of autophagy.

hsa_circ_0081343 served as an RNA-binding protein (RBP) sponge. RNA binding motif protein 8A (Rbm8a) was directly bound to hsa_circ_0081343 in the cytoplasm, while knockdown of hsa_circ_0081343 facilitated Rbm8a localization in the nucleus. We also identified Rbm8a as a potential import cargo for Importin13 (Ipo13), which transported Rbm8a across the nuclear membrane into the nucleus. Ipo13 recognized Rbm8a via a functional nuclear localization signal (NLS). Furthermore, the mechanistic study revealed that hsa_circ_0081343-mediated nuclear translocation of Rbm8a activated trophoblast autophagy.

Our results suggest that hsa_circ_0081343 could bind to RBP and the interaction between hsa_circ_0081343 and Rbm8a participate in regulating autophagy. These findings offer novel molecular targets and insights for a potential therapeutic strategy against FGR.