HNRNPA2B1-mediated m6A modification enhances lncRNA NORHA stability to control granulosa cell functionsOACSCDCSTPCD
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 m6Adependent regulatory mechanism governing NORHA expression in sGCs.
Chun-Xue Zhou;Si-Qi Wang;Ji-Yu Zhang;Xing Du;Qi-Fa Li
College of Animal Science and Technology,Nanjing Agricultural University,Nanjing,Jiangsu 210095,ChinaCollege of Animal Science and Technology,Nanjing Agricultural University,Nanjing,Jiangsu 210095,ChinaCollege of Animal Science and Technology,Nanjing Agricultural University,Nanjing,Jiangsu 210095,ChinaCollege of Animal Science and Technology,Nanjing Agricultural University,Nanjing,Jiangsu 210095,ChinaCollege of Animal Science and Technology,Nanjing Agricultural University,Nanjing,Jiangsu 210095,China
农业科技
LncRNA NORHAm6A modificationHNRNPA2B1FoxO1Sow granulosa cells
《Zoological Research》 2025 (3)
P.722-732,11
supported by the National Natural Science Foundation of China(32072693)Fundamental Research Funds for the Central Universities(KYLH2025010)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX24-0994)。
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