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MeRIP-seq数据分析与验证揭示了m⁶A修饰的环状RNA在内蒙古绒山羊次级毛囊细胞凋亡中的调控作用。

MeRIP-seq data analysis and validation reveal the regulatory role of mA modified circRNAs in the apoptosis of secondary hair follicle cells in Inner Mongolia cashmere goats.

作者信息

Zhang Ru, Liang Jiayue, Liu Zhaomin, Chang Jiale, Zhang Junjie, Zhang Zhanxiong, Li Rui, Zhao Wei, Deng Yongyuan, Xiao Hongmei

机构信息

College of Life Sciences, Inner Mongolia Agricultural University, Hohhot 010010, China; Inner Mongolia Autonomous Region Key Laboratory of Biomanufacturing, Hohhot 010010, China.

Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Comp Biochem Physiol Part D Genomics Proteomics. 2025 Jun;54:101419. doi: 10.1016/j.cbd.2025.101419. Epub 2025 Jan 12.

DOI:10.1016/j.cbd.2025.101419
PMID:39837064
Abstract

As a widely epigenetic modification, mA (N-methyladenosine, mA) can regulate the degradation, translation, and other biological functions of circRNAs through dynamic reversible processes. It plays an important role in regulating the life activities of biological organisms, particularly in cell differentiation, apoptosis, embryonic development, stress response, and innate immunity. In this study, bioinformatics analysis, qRT-PCR identification, FISH subcellular localization, and ceRNA network construction were performed on mA modified circRNAs regulating the apoptosis of secondary hair follicle cells of Inner Mongolia Albas white cashmere goats based on the skin mA sequencing data of secondary hair follicles in anagen and catagen. The results showed that 8 mA modified circRNAs regulating the cell apoptosis of secondary hair follicles, namely circRNA_2130, circRNA_0013, circRNA_1203, circRNA_1462, circRNA_1242, circRNA_2308, circRNA_2654 and circRNA_1442 were identified, and they are respectively derived from ANGEL2, APP, GKAP1, HNRNPC, PTBP3, NUCB1, SNRK and ZNF609 genes. Among them, circRNA_0013, circRNA_1442 and circRNA_1462 were located in the cytoplasm of the secondary hair follicle papilla, while circRNA_1203, circRNA_1242, circRNA_2130, circRNA_2308 and circRNA_2654 were located in the nucleus. There are complex and diverse regulatory relationships among 8 circRNAs, with each circRNA targeting one or more miRNAs, revealing that each mA circRNA can exert regulatory effects through multiple potential miRNA-mRNA axes, to regulate the apoptosis of secondary hair follicle cells of cashmere goats during the growth cycles. This result provides a direction for further elucidating the regulatory mechanism of mA modified circRNAs in cashmere growth and exploring biomarkers.

摘要

作为一种广泛存在的表观遗传修饰,N6-甲基腺嘌呤(mA)可通过动态可逆过程调控环状RNA(circRNA)的降解、翻译及其他生物学功能。它在调节生物机体的生命活动中发挥着重要作用,尤其在细胞分化、凋亡、胚胎发育、应激反应和先天免疫方面。本研究基于内蒙古阿尔巴斯白绒山羊次生毛囊生长期和退行期皮肤的mA测序数据,对调控次生毛囊细胞凋亡的mA修饰circRNA进行了生物信息学分析、qRT-PCR鉴定、FISH亚细胞定位及ceRNA网络构建。结果表明,鉴定出8个调控次生毛囊细胞凋亡的mA修饰circRNA,即circRNA_2130、circRNA_0013、circRNA_1203、circRNA_1462、circRNA_1242、circRNA_2308、circRNA_2654和circRNA_1442,它们分别来源于ANGEL2、APP、GKAP1、HNRNPC、PTBP3、NUCB1、SNRK和ZNF609基因。其中,circRNA_0013、circRNA_1442和circRNA_1462位于次生毛囊乳头细胞的细胞质中,而circRNA_1203、circRNA_1242、circRNA_2130、circRNA_2308和circRNA_2654位于细胞核中。8个circRNA之间存在复杂多样的调控关系,每个circRNA靶向一个或多个miRNA,表明每个mA circRNA可通过多个潜在的miRNA-mRNA轴发挥调控作用,以调节绒山羊次生毛囊细胞在生长周期中的凋亡。该结果为进一步阐明mA修饰circRNA在绒毛生长中的调控机制及探索生物标志物提供了方向。

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