Long intergenic non-coding RNAs (lincRNAs) have been proved to be involved in regulating female reproduction. However, to what extent lincRNAs are involved in ovarian functions and fertility is incompletely understood. Here we show that a lincRNA, NORFA is involved in granulosa cell apoptosis, follicular atresia and sow fertility. We found that NORFA was down-regulated during follicular atresia, and inhibited granulosa cell apoptosis. NORFA directly interacted with miR-126 and thereby preventing it from binding to TGFBR2 3′-UTR. miR-126 enhanced granulosa cell apoptosis by attenuating NORFA-induced TGF-β signaling pathway. Importantly, a breed-specific 19-bp duplication was detected in NORFA promoter, which proved association with sow fertility through enhancing transcription activity of NORFA by recruiting transcription factor NFIX. In summary, our findings identified a candidate lincRNA for sow prolificacy, and provided insights into the mechanism of follicular atresia and female fertility.

长基因间非编码RNA（lincRNA）已被证明参与调节雌性生殖。然而，lincRNA 在多大程度上参与卵巢功能和生育力尚不完全清楚。在这里，我们证明 lincRNA NORFA参与颗粒细胞凋亡、卵泡闭锁和母猪生育力。我们发现NORFA在卵泡闭锁期间下调，并抑制颗粒细胞凋亡。 NORFA 直接与 miR-126 相互作用，从而阻止其与TGFBR2 3'-UTR 结合。 miR-126 通过减弱NORFA诱导的 TGF-β 信号通路增强颗粒细胞凋亡。重要的是，在NORFA启动子中检测到品种特异性的 19 bp 重复，证明该重复通过招募转录因子 NFIX 来增强NORFA的转录活性，从而与母猪繁殖力相关。总之，我们的研究结果确定了母猪繁殖力的候选 lincRNA，并为卵泡闭锁和雌性生育力的机制提供了见解。