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The circular RNA circbabo(5,6,7,8S) regulates lipid metabolism and neuronal integrity in Drosophila

ABSTRACT: Circular RNAs (circRNAs) are widely expressed in eukaryotes. However, only a subset has been functionally characterized. Here we report that the circRNA circbabo(5,6,7,8S) regulates lipid metabolism and neuronal integrity in Drosophila. We show that circbabo(5,6,7,8S) is derived from the babo pre-mRNA by back-splicing, and is widely distributed in Drosophila tissues. Depletion of circbabo(5,6,7,8S) in the fat body and neurons, respectively, causes elevated lipid droplet (LD) accumulation, and 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 a reduction in ATP levels and upregulation of ROS. Moreover, we provide evidence that circbabo(5,6,7,8S) encodes the protein circbabo(5,6,7,8S)-p, which inhibits the TGF-β signaling pathway by interfering with the assembly of babo/put heterodimer complex. Lastly, we show that the ROS/JNK/SREBP signaling cascade is implicated in the LD accumulation, neurodegeneration, and shortened lifespan phenotypes elicited by circbabo(5,6,7,8S) depletion. Thus, our study demonstrates the physiological role of the protein-coding circRNA circbabo(5,6,7,8S) in regulating lipid metabolism and neuronal integrity.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE271420 | GEO | 2025/02/13

REPOSITORIES: GEO

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