hnrnpa2b1介导的m6A修饰增强lncRNA NORHA稳定性以控制颗粒细胞功能。

IF 4 1区 生物学 Q1 ZOOLOGY
Chun-Xue Zhou, Si-Qi Wang, Ji-Yu Zhang, Xing Du, Qi-Fa Li
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引用次数: 0

摘要

NORHA是一种长链非编码RNA (lncRNA),通过触发颗粒细胞(GCs)凋亡而成为母猪卵泡闭锁的关键诱导剂。然而,n6 -甲基腺苷(m6A)-最丰富的RNA修饰-对其的调控仍未解决。本研究发现NORHA是母猪GCs (sGCs)中m6A读取器HNRNPA2B1的功能靶点。RNA修饰位点的转录组全图谱显示,NORHA上广泛富集m6A, HNRNPA2B1直接结合到转录本上,并通过修饰多个m6A位点(包括A261、A441和A919)增强其稳定性。HNRNPA2B1通过激活NORHA-FoxO1轴抑制17β-雌二醇(E2)生物合成,促进sGC凋亡。fox01随后抑制细胞色素P450家族19亚家族A成员1 (CYP19A1)的表达,CYP19A1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NORHA在sGCs中的表达和活性。这项研究强调了一个重要的m6a依赖性调控机制,调控了sGCs中NORHA的表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
HNRNPA2B1-mediated m6A modification enhances lncRNA NORHA stability to control granulosa cell functions.

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.

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来源期刊
Zoological Research
Zoological Research Medicine-General Medicine
CiteScore
7.60
自引率
10.20%
发文量
1937
审稿时长
8 weeks
期刊介绍: Established in 1980, Zoological Research (ZR) is a bimonthly publication produced by Kunming Institute of Zoology, the Chinese Academy of Sciences, and the China Zoological Society. It publishes peer-reviewed original research article/review/report/note/letter to the editor/editorial in English on Primates and Animal Models, Conservation and Utilization of Animal Resources, and Animal Diversity and Evolution.
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