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 modificatio...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.展开更多
目的:研究肥胖小鼠及正常小鼠不同周龄下丘脑组织SH2B1(adapter protein with a Src-homology 2 domain),细胞因子信号转导抑制蛋白3(the suppressor of cytokine signaling-3,SOCS3),蛋白质酪氨酸磷酸酶1B(proteintyrosine phosphatase...目的:研究肥胖小鼠及正常小鼠不同周龄下丘脑组织SH2B1(adapter protein with a Src-homology 2 domain),细胞因子信号转导抑制蛋白3(the suppressor of cytokine signaling-3,SOCS3),蛋白质酪氨酸磷酸酶1B(proteintyrosine phosphatase 1B,PTP1B)和神经肽Y(neturopetide Y,NPY)表达的变化规律及其与血清瘦素及胰岛素水平的关系。方法:选用健康C57BL/6乳鼠制作肥胖动物模型,计算Lee’s指数及稳态模型胰岛素抵抗指数。荧光定量RT-PCR法检测下丘脑SH2B1,SOCS3及PTP1B mRNA表达量,Western印迹检测下丘脑SH2B1和NPY蛋白表达量。结果:与同周龄对照组小鼠相比,肥胖组小鼠下丘脑组织SH2B1 mRNA表达减少,SOCS3及PTP1B mRNA表达增加;Western印迹结果显示:肥胖组小鼠SH2B1蛋白表达水平较对照组下降,NPY表达升高。直线相关分析显示:血清瘦素和血清空腹胰岛素水平与SH2B1 mRNA表达呈负相关,与SOCS3及PTP1B mRNA表达正相关。结论:SH2B1,SOCS3,PTP1B及NPY是肥胖发生、发展过程中的关键因子。展开更多
基金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)。
文摘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.
文摘目的:研究肥胖小鼠及正常小鼠不同周龄下丘脑组织SH2B1(adapter protein with a Src-homology 2 domain),细胞因子信号转导抑制蛋白3(the suppressor of cytokine signaling-3,SOCS3),蛋白质酪氨酸磷酸酶1B(proteintyrosine phosphatase 1B,PTP1B)和神经肽Y(neturopetide Y,NPY)表达的变化规律及其与血清瘦素及胰岛素水平的关系。方法:选用健康C57BL/6乳鼠制作肥胖动物模型,计算Lee’s指数及稳态模型胰岛素抵抗指数。荧光定量RT-PCR法检测下丘脑SH2B1,SOCS3及PTP1B mRNA表达量,Western印迹检测下丘脑SH2B1和NPY蛋白表达量。结果:与同周龄对照组小鼠相比,肥胖组小鼠下丘脑组织SH2B1 mRNA表达减少,SOCS3及PTP1B mRNA表达增加;Western印迹结果显示:肥胖组小鼠SH2B1蛋白表达水平较对照组下降,NPY表达升高。直线相关分析显示:血清瘦素和血清空腹胰岛素水平与SH2B1 mRNA表达呈负相关,与SOCS3及PTP1B mRNA表达正相关。结论:SH2B1,SOCS3,PTP1B及NPY是肥胖发生、发展过程中的关键因子。
