基础医学与临床 ›› 2026, Vol. 46 ›› Issue (7): 982-989.doi: 10.16352/j.issn.1001-6325.2026.07.0982

• 研究论文 • 上一篇    下一篇

富含AU元件(AREs)及其结合蛋白协同发育程序

辛明君, 霍悦, 王芳*   

  1. 中国医学科学院北京协和医学院 基础医学研究所 重大疾病共性机制研究国家重点实验室, 北京 100005
  • 收稿日期:2026-03-19 修回日期:2026-05-19 发布日期:2026-06-23
  • 通讯作者: *wo_wfang@hotmail.com

AU-rich elements(AREs) and their binding proteins coordinate developmental programs

XIN Mingjun, HUO Yue, WANG Fang*   

  1. State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100005,China
  • Received:2026-03-19 Revised:2026-05-19 Published:2026-06-23
  • Contact: *wo_wfang@hotmail.com

摘要: 目的 探讨富含腺嘌呤尿嘧啶元件(AREs)及其结合蛋白(AREBPs)在基因转录后调控及翻译过程中的潜在协同作用。方法 利用自定义算法提取人与小鼠全基因组3'UTR区的ARE核心基序;整合Postar3数据库、GEO公共CLIP-seq数据及自主建库clip-seq和PrismNet深度学习预测结果,获取AREBPs的结合位点;采用Fisher精确检验计算特定AREBPs在组织特异性基因中的富集度(odds ratio);结合GTEx数据库及特定组织发育RNA-seq数据集(肾脏发育GSE100859),分析AREBPs与靶基因的共表达模式。结果 成功提取了人与小鼠保守的3'UTR AREs全基因组图谱;发现特定AREBPs在肌肉、大脑、肾脏和心脏的特异性基因中呈现显著的结合富集(P<0.05);表达谱分析显示,在组织发育(如肾脏发育)过程中,带有AREs的基因与无AREs的基因在表达模式上存在显著差异。结论 AREs及其结合蛋白在不同组织的转录后调控中发挥着高度特异性的作用,本研究为理解组织发育与稳态维持的RNA调控机制提供了重要的生物信息学依据。

关键词: 增强型紫外交联免疫共沉淀测序(eCLIP-seq), 富含腺嘌呤尿嘧啶元件(AREs), 组织发育, RNA结合蛋白, 多组学, 数据库

Abstract: Objective To explore the potential synergistic roles of AU-rich elements (AREs) and their binding proteins (AREBPs) in post-transcriptional regulation and the translation process. Methods A customized algorithm was utilized to extract the core ARE motifs within the 3'UTR regions across human and mouse genomes.The binding sites of AREBPs were identified by integrating data from the Postar3 database, public CLIP-seq datasets from GEO.Independently constructed CLIP-seq database and PrismNet deep learning predictions. Fisher's exact test was applied to calculate the enrichment degree (odds ratio) of specific AREBPs in tissue-specific genes.The co-expression patterns between AREBPs and target genes were analyzed by combining the GTEx database and tissue-specific developmental RNA-seq datasets (e.g., kidney development dataset GSE100859). Results A comprehensive genome-wide map of conserved 3'UTR AREs in humans and mice was successfully generated.Specific AREBPs exhibited significant binding enrichment (P<0.05) in tissue-specific genes associated with muscle, brain, kidney and heart.Expression profiling analysis revealed that during tissue development (such as kidney development), genes containing AREs showed significantly different expression patterns compared to those without AREs. Conclusions AREs and their binding proteins play a highly specific function in kidney development, genes containing AREs showed significantly different expression patterns as compared to those without AREs. Conclusions AREs and their binding proteins play a highly specific role in post-transcriptional regulation across different tissues. This study provides a crucial bioinformatics evidence for understanding the RNA regulatory mechanisms underlying tissue development and homeostasis maintenance.

Key words: enhanced UV crosslinking immunoprecipitation-sequencing(eCLIP-seq), AU-rich elements(AREs), tissue develop-ment, RNA-binding proteins, multi-omics, database

中图分类号: