Circular RNA circNID2 Promotes Bovine Adipogenesis via miR-339a/NNAT

Abstract

Adipose tissue development significantly influences meat quality and economic traits in beef cattle. In this study, we identified a novel circular RNA derived from two exons (exons 3 and exons 9) of the NID2 gene, designated as circNID2, which exhibits high structural stability and marked upregulation during bovine adipocyte differentiation. Functional assays demonstrated that circNID2 suppresses the proliferation and apoptosis of bovine preadipocytes while robustly promoting adipogenic differentiation and lipid accumulation. Although containing several putative open reading frames, circNID2 lacks protein-coding potential. Mechanistically, circNID2 functions as a competing endogenous RNA by sponging miR-339a, thereby relieving the post-transcriptional repression of its downstream target, Neuronatin (NNAT). Functional rescue experiments further validated that circNID2 partially neutralizes the regulatory effects of miR-339a on preadipocyte proliferation, apoptosis, and differentiation. Collectively, these findings demonstrate that circNID2 regulates bovine preadipocyte function through the newly established circNID2/miR-339a/NNAT axis. This study provides novel insights into the post-transcriptional mechanisms governing mammalian adipogenesis and highlights circNID2 as a potential molecular target for improving fat deposition traits in cattle.