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.

长期的基因间非编码RNA（lincRNA）已被证明参与调节女性生殖。但是，人们对lincRNA在何种程度上参与卵巢功能和生育能力尚不完全了解。在这里，我们显示了一个lincRNA，NORFA参与了颗粒细胞凋亡，卵泡闭锁和母猪繁殖力。我们发现NORFA在滤泡闭锁过程中被下调，并抑制颗粒细胞凋亡。NORFA与miR-126直接相互作用，从而阻止其与TGFBR2 3'-UTR结合。miR-126通过减弱NORFA诱导的TGF-β信号通路来增强颗粒细胞凋亡。重要的是，在NORFA中检测到特定于品种的19 bp复制启动子，通过募集转录因子NFIX增强NORFA的转录活性，证明与母猪育性相关。总而言之，我们的发现确定了母猪繁殖力的候选lincRNA，并为卵泡闭锁和女性生育力的机制提供了见识。