Super-Enhancer-Associated circ RHOQ Regulates Intramuscular Fat Deposition by Modulating the miR-5093/ IRF5 Axis

Circular RNAs (circRNAs) play a crucial role in post-transcriptional regulation during the development and physiology of mammals. However, the role of superenhancer (SE)-associated circRNAs (SE-circRNAs) in adipogenesis remains largely unexplored. In this study, RNA and H3K27ac chromatin immunoprecipitation Sequencing analyses of yak muscle tissues with varying IMF contents were performed, and 81 differentially expressed SE-circRNAs were identified in the high IMF (intramuscular fat) group. Among them, circRHOQ was notably associated with SEs, with H3K27ac signals enriched at its genomic locus. Enhancer activity assays identified two key regulatory regions (chr9:49134487-49135239 and chr9:49136018-49136614) with significant transcriptional activation. Treatment with JQ-1 suppressed circRHOQ expression, confirming that circRHOQ is an SE-driven regulatory circRNA. Functional assays validated that circRHOQ is a cytoplasmic circRNA that promotes yak intramuscular preadipocyte adipogenic differentiation, as indicated by the increased lipid accumulation, triacylglycerol content, and adipogenic gene expression. Mechanistically, circRHOQ acts as a competing endogenous RNA by binding to miR-5093, thereby derepressing its target IRF5 and promoting adipogenesis. Dual-luciferase assays validated the direct interactions among circRHOQ, miR-5093, and IRF5. This study revealed that circRHOQ promotes yak IMF development via the SE-circRHOQ/miR-5093/IRF5 axis, thus providing a basis for further investigation into IMF deposition and improvement of high-altitude livestock breeds.

circRHOQ; histone modification; intramuscular fat deposition; superenhancers.