NORFA, long intergenic noncoding RNA, maintains sow fertility by inhibiting granulosa cell death

Xing Du et al. show that long intergenic non-coding RNA (lincRNA) NORFA maintains sow fertility by inhibiting apoptotic death of granulosa cells through the TGF-beta signaling pathway. A breed-specific 19-bp duplication suggests that transcription factor NFIX may enhance the transcription of NORFA, providing insights into the role of lincRNAs for female fertility. 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-beta 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.