RBM15 affects mitophagy in intracerebral hemorrhage by promoting E2F1 nuclear translocation via NXF1

Nuclear mRNA transport is essential for maintaining mRNA homeostasis and normal cellular functions; however, the mechanisms regulating the nuclear transport of E2F transcription factor 1 (E2F1) mRNA remain poorly understood. In this study, we show that the nuclear RNA transport factor 1 (NXF1) is upregulated in Hemin-treated HT22 cells and intracerebral hemorrhage (ICH) mice, suggesting its involvement in ICH pathogenesis. NXF1 knockdown exerted a protective effect against Hemin-induced inflammatory responses in HT22 cells. Consistently, NXF1 downregulation ameliorated neurological deficits, reduced cell death, and decreased cytokine levels in vivo. Mechanistically, NXF1-mediated neuroprotection was associated with mitophagy induction. Collectively, our findings provide novel insights into ICH progression and identify the RBM15/NXF1/E2F1 axis as a potential target for ICH intervention.