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HNRNPA2B1-mediated m6A modification enhances lncRNA NORHA stability to control granulosa cell functions
Chun-Xue Zhou1, Si-Qi Wang1, Ji-Yu Zhang1
1College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.
Zoological Research
|May 23, 2025
Summary
N6-methyladenosine (m6A) modification regulates NORHA, a long non-coding RNA, in sow granulosa cells. This RNA modification impacts follicular atresia by controlling cell apoptosis and hormone biosynthesis.
Area of Science:
- Reproductive Biology
- Epigenetics
- Molecular Endocrinology
Background:
- NORHA, a long non-coding RNA (lncRNA), induces follicular atresia in sows via granulosa cell (GC) apoptosis.
- The regulatory role of N6-methyladenosine (m6A) modification on NORHA is currently unknown.
Purpose of the Study:
- To investigate the regulatory mechanism of NORHA by m6A modification in sow GCs (sGCs).
- To elucidate the role of the m6A reader HNRNPA2B1 in NORHA regulation and its impact on sGC function.
Main Methods:
- Transcriptome-wide mapping of RNA modification sites.
- RNA immunoprecipitation (RIP) assays to confirm HNRNPA2B1 binding to NORHA.
- Analysis of NORHA-FoxO1 axis and its effect on CYP19A1 expression and 17β-estradiol (E2) biosynthesis.
Main Results:
- NORHA was identified as a direct target of the m6A reader HNRNPA2B1 in sGCs.
- HNRNPA2B1 binds to NORHA, enhancing its stability through m6A modification, and activates the NORHA-FoxO1 axis.
- This axis suppresses E2 biosynthesis by repressing CYP19A1 and promotes sGC apoptosis.
- HNRNPA2B1 mediates METTL3-dependent m6A modification, influencing NORHA expression and activity.
Conclusions:
- This study reveals an m6A-dependent regulatory pathway governing NORHA expression in sGCs.
- HNRNPA2B1-mediated m6A modification of NORHA plays a crucial role in regulating follicular atresia by affecting GC apoptosis and steroidogenesis.
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