The circular RNA circbabo(5,6,7,8S) regulates lipid metabolism and neuronal integrity via TGF-β/ROS/JNK/SREBP signaling axis in Drosophila

作者：Jie Sheng, Xuemei Zhang, Weihong Liang, Junfang Lyu, Bei Zhang, J. Min, Aimin Xu, Xingyu Xu, Jennifer W. Li, Jian‐Liang Li, Rui Zhou, Wei Liu · 发表于：BMC Biology · 年份：2025 · DOI：10.1186/s12915-025-02175-1 · 被引用次数：7 · 研究领域：Lipid metabolism and biosynthesis、Hippo pathway signaling and YAP/TAZ、Circular RNAs in diseases

BACKGROUND: Lipid droplets (LDs) are dynamic cytoplasmic lipid-storing organelles that play a pivotal role in maintaining cellular energy balance, lipid homeostasis, and metabolic signaling. Dysregulation of lipid metabolism, particularly excessive lipogenesis, contributes to the abnormal accumulation of LDs in the nervous system, which is associated with several neurodegenerative diseases. Circular RNAs (circRNAs) are a new class of non-coding and regulatory RNAs that are widely expressed in eukaryotes. However, only a subset has been functionally characterized. Here, we identified and functionally characterized a new circular RNA circbabo(5,6,7,8S) that regulates lipogenesis and neuronal integrity in Drosophila melanogaster. RESULTS: circbabo(5,6,7,8S) is derived from the babo locus which encodes the type I receptor for transforming growth factor β (TGF-β). Depletion of circbabo(5,6,7,8S) in flies causes elevated lipid droplet accumulation, progressive photoreceptor cell loss and shortened lifespan, phenotypes that are rescued by restoring circbabo(5,6,7,8S) expression. In addition, RNA-seq and epistasis analyses reveal that these abnormalities are caused by aberrant activation of the SREBP signaling pathway. Furthermore, circbabo(5,6,7,8S)-depleted tissues display enhanced activation of the TGF-β signaling pathway and compromised mitochondrial function, resulting in upregulation of reactive oxygen species (ROS). Moreover, we provide evidence that circbabo(5,6,7,8S) encodes...