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Granulosa cell (GC) is a critical somatic component of ovarian follicles to support oocyte development, while the regulatory role of long noncoding RNA (lncRNA) in GCs is largely unknown. Here, we identified a down-regulated lncRNA  ZNF674-AS1  in GCs from patients with biochemical premature ovarian insufficiency (bPOI), and its expression correlates with serum levels of clinical ovarian reserve indicators. Functional experiments showed that  ZNF674-AS1  is induced by energy stress, and regulates the proliferation and glycolysis of GCs, which possibly leads to follicular dysfunction. Mechanistically, low-expressed  ZNF674-AS1  reduced the enzymatic activity of aldolase A (ALDOA), concomitant with promoting the association between ALDOA and v-ATPase to activate the lysosome localized AMP-activated protein kinase (AMPK). These findings identified a new lncRNA–ALDOA complex through which  ZNF674-AS1  exerts its functions, expanding the understanding of epigenetic regulation of GCs function and POI pathogenesis.

LncRNA ZNF674-AS1 regulates granulosa cell glycolysis and proliferation by interacting with ALDOA