动物脂肪细胞分化过程中全转录组3'-UTR动态变化研究

Study on dynamic changes of global transcriptome 3’-UTR during preadipocyte differentiation in animals

基因转录调控,涉及3’-端非翻译区(3’-UTR)序列长度和组成动态调节,直接参与m RNA稳定性、亚细胞定位和翻译效率等生物学过程。研究表明,复杂性状(包括动物生产性能、人类疾病等)与3’-UTR密切相关。然而,动物前脂肪细胞分化过程中3’-UTR动态变化模式和规律鲜有报道。研究运用生物信息学方法,通过分析四种动物(鸡、鸭、猪和小鼠)不同分化时期前脂肪细胞转录组测序(RNA-seq)数据,检测并比较选择性多聚腺苷酸化动态变化。结果发现,京海黄鸡、北京鸭前脂肪细胞和小鼠3T3-L1细胞在分化过程中,存在3’-UTR长度动态变化,而长白猪中无变化。前脂肪细胞分化过程中,北京鸭和小鼠倾向于使用3’-UTR更短转录本;而京海黄鸡倾向于在分化前期和后期分别使用3’-UTR更长和更短转录本。基因功能富集分析发现,3’-UTR长度显著差异基因主要富集于脂肪细胞分化,脂质代谢,细胞生长和迁移等信号通路。综上,不同动物前脂肪细胞分化过程中,存在基因3’-UTR长度动态和规律变化,并同脂肪生成和脂类物质代谢相关,可为进一步研究脂肪生长发育分子调控机制提供新思路和参考。

Transcriptional regulation, including the dynamic regulation of sequence length and composition of the 3’-untranslated region(3’-UTR), directly affects biological processes, such as mRNA stability, subcellular localization and translational efficiency. Complex traits(animal production performance and human diseases) are closely related to 3’-UTR, too. However, the dynamic changes of 3’-UTR during the differentiation of animal preadipocytes remain less studied. Here, the transcriptome sequencing(RNA-seq) data were compared at different stages of preadipocyte differentiation from four animals(chicken, duck, pig and mouse), to detect alternative polyadenylation using Bioinformatics methods. Dynamic changes of 3’-UTRat the global transcriptome level were discovered during differentiation of the Jinghai Yellow chicken and Pekin duck preadipocytes, and mouse 3T3-L1 cells as well, but not for the Landrace pig. During preadipocyte differentiation, Pekin ducks and mice tended to use shorter 3’-UTR transcripts, whereas Jinghai Yellow chicken tended to use transcripts with longer 3’-UTR in the early stage, but shorter 3’-UTR in the later stage. Functional enrichment analysis revealed that genes with different 3’-UTR lengths were mainly involved in adipocyte differentiation, lipid metabolism, cell growth and migration signaling pathways. Taken together, the dynamic changes of global 3’-UTR during preadipocyte differentiation in different animals were discovered, which were functionally related to adipogenesis and lipid metabolism. New insightson were provided to further investigate the molecular mechanism of adipose tissue growth and development.