Zhou Chun-Xue, Wang Si-Qi, Zhang Ji-Yu, Du Xing, Li Qi-Fa
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China. E-mail:
Zool Res. 2025 May 18;46(3):722-732. doi: 10.24272/j.issn.2095-8137.2024.378.
NORHA, a long non-coding RNA (lncRNA), serves as a key inducer of follicular atresia in sows by triggering granulosa cells (GCs) apoptosis. However, its regulation by N6-methyladenosine (m6A)-the most abundant RNA modification-remains unresolved. This study identified NORHA as a functional target of the m6A reader HNRNPA2B1 in sow GCs (sGCs). Transcriptome-wide mapping of RNA modification sites revealed extensive m6A enrichment on NORHA, with HNRNPA2B1 binding directly to the transcript and enhancing its stability via modification of multiple m6A sites, including A261, A441, and A919. HNRNPA2B1 suppressed 17β-estradiol (E2) biosynthesis and promoted sGC apoptosis by activating the NORHA-FoxO1 axis. FoxO1 subsequently repressed expression of cytochrome P450 family 19 subfamily A member 1 (CYP19A1), which encodes the enzyme essential for E2 biosynthesis. Additionally, HNRNPA2B1 functioned as a critical mediator of METTL3-dependent m6A modification, modulating NORHA expression and activity in sGCs. This study highlights an important m6A-dependent regulatory mechanism governing NORHA expression in sGCs.
NORHA是一种长链非编码RNA（lncRNA），通过触发颗粒细胞（GCs）凋亡，作为母猪卵泡闭锁的关键诱导因子。然而，其受N6-甲基腺苷（m6A，最丰富的RNA修饰）的调控仍未得到解决。本研究确定NORHA是母猪颗粒细胞（sGCs）中m6A阅读蛋白HNRNPA2B1的功能靶点。全转录组RNA修饰位点图谱显示NORHA上广泛富集m6A，HNRNPA2B1直接与该转录本结合，并通过修饰多个m6A位点（包括A261、A441和A919）来增强其稳定性。HNRNPA2B1通过激活NORHA-FoxO1轴抑制17β-雌二醇（E2）的生物合成并促进sGC凋亡。FoxO1随后抑制细胞色素P450家族19亚家族A成员1（CYP19A1）的表达，该基因编码E2生物合成所必需的酶。此外，HNRNPA2B1作为METTL3依赖性m6A修饰的关键介质，调节sGCs中NORHA的表达和活性。本研究突出了一种重要的依赖m6A的调控机制，该机制控制sGCs中NORHA的表达。
