嵌合RNA的形成机制及生物学意义  

The Formation Mechanism and Functional Implication of Chimeric RNAs

作　　者：陈晨 秦付军 唐悦[1] CHEN Chen;QIN Fu-Jun;TANG Yue(Department of Microbiology and Immunology,School of Basic Medical Sciences,Zhengzhou University,Zhengzhou 450001;Molecular Phathology Center,Academy of Medical Science,Zhengzhou University,Zhengzhou 450052,China;Translational Medicine Platform,Academy of Medical Science,Zhengzhou University,Zhengzhou 450052,China;State Key Laboratory of Esophageal Cancer Prevention&Treatment,Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学基础医学院微生物学与免疫学系,郑州450001 [2]郑州大学医学科学院分子病理中心,郑州450052 [3]郑州大学医学科学院转化医学平台,郑州450052 [4]郑州大学省部共建食管癌防治国家重点实验室,郑州450052

出　　处：《中国生物化学与分子生物学报》2022年第7期839-848,共10页Chinese Journal of Biochemistry and Molecular Biology

基　　金：河南省重点研发与推广专项(科技攻关)项目(No.202102310097);国家自然科学基金面上项目(No.81972421);国家自然科学基金(NSFC)-河南省联合项目(No.U2004135)资助。

摘　　要：传统观念认为,嵌合RNA只是由染色体重排导致的基因融合,且融合基因及其产物(RNA和蛋白质)曾被认为是癌症的独有特征。然而,随着测序技术的进步和生物信息学软件工具的开发,通过对RNA-Seq数据库分析,越来越多的嵌合RNA被分离和鉴定出来。近年的研究表明,嵌合RNA并不是癌症所特有的现象,它广泛存在于人类多种正常组织和细胞中。除了染色体重排之外,嵌合RNA还有多种不同的分子形成机制,包括相邻基因的顺式剪接和反式剪接等。未发生染色体改变的嵌合RNA在转录水平上受到调控,从而呈现出独特的调控模式,其失调可能影响细胞分化并诱导肿瘤的发生。此外,嵌合RNA还发挥特定的生理功能,包括影响正常细胞生长和迁移能力,调控细胞周期及凋亡。通过影响染色体重排从而诱导基因组畸变,亦可作为潜在的竞争性内源RNA,以及影响干细胞的分化等。了解嵌合RNA在组织和细胞发育不同阶段的特异性表达,将有助于发掘潜在的临床诊疗生物标志物。深入且准确地对嵌合RNA的组织学图谱进行研究,可能实现从崭新的视角对特定细胞类型进行嵌合RNA治疗。越来越多的实验数据表明,嵌合RNA广泛存在于癌症和正常组织中,且具有重要的生理功能,其表达水平和模式也是高等动物拓展基因组功能的方式之一.Traditionally,chimeric RNA is thought to be generated by chromosome rearrangement,and its products(RNAs and proteins)were once considered as unique features of cancer.However,with the advancement of next-generation sequencing technologies and the development of bioinformatics software tools,increasing numbers of chimeric RNAs are being identified from various RNA-Seq database.Recently,numerous chimeric RNAs were discovered in human normal tissues and cell lines,with physiological functions.Besides chromosome rearrangement,chimeric RNAs are formed by different molecular mechanisms,including trans-splicing,cis-splicing of adjacent genes.Chimeric RNAs,without chromosomal changes,are regulated at the transcriptional level,and they show specific physiological functions and regulation patterns.Their dysregulation may induce cell differentiation and tumorogenisis.In addition,chimeric RNAs also play roles in normal cell growth and/or migration,cell cycle and apoptosis,induce genomic aberration by influencing chromosome rearrangement,act as potential competitive endogenous RNA,and influence stem cell differentiation.The expression of chimeric RNAs in specific tissues and cell development stages has the potential to be used as diagnostic and therapeutic biomarkers.Histological mapping studies can improve the specificity of treatment for unique cell types,and the chimeric RNA provides a new perspective to achieve this goal.The widespread existence of chimeric RNAs suggests that they may extend the diversity of genomes in human and higher animals.

关 键 词：染色体重排 嵌合RNA 顺式剪接 反式剪接 相邻基因顺式剪接 

分 类 号：Q752[生物学—分子生物学]