长非编码RNA的表达调控机制

The Regulation Mechanism of Long Non-coding RNA Expression

长非编码RNA(long non-coding RNA,lncRNA)是一类长度超过200 nt核苷酸转录本。研究表明,lncRNA可以调控细胞分化、免疫反应和细胞凋亡等生理过程,在多种代谢性疾病和癌症的发生与发展中发挥重要作用。在上述生理或病理过程中,lncRNA通常作为基因表达调控因子,引起下游靶基因异常表达,但lncRNA在这些疾病中本身的差异性表达是如何被调控的,尚不清楚。LncRNA的表达同基因组其他基因一样,在DNA水平、转录水平和转录后水平均受到调控。DNA水平的调控是基因表达调控最主要的环节。研究表明,8号染色体片段丢失和DNA拷贝数变异是肿瘤常见的基因事件。这些缺失或拷贝数异常增加的DNA片段中,存在lncRNA的基因;除了DNA片段丢失和拷贝数变异,还包括启动子区域甲基化、组蛋白修饰以及DNA空间构象改变等。在转录水平上,转录因子结合并激活启动子是最常见的机制。转录后水平上的调控主要指对lncRNA稳定性的调节。有研究发现,微RNA(micro RNA,miRNA)可以结合lncRNA的3′UTR端非翻译区(untranslated region,UTR),降低lncRNA稳定性;另外,lncRNA的m^(6)A甲基化修饰同样会影响lncRNA稳定和功能。本文将围绕DNA水平、转录水平和转录后水平3个方面的调控机制进行阐述,以期为后续lncRNA的调控机制研究提供一定的参考。

Long non-coding RNAs(lncRNAs) are a class of nucleotide transcripts over 200 nt in length.Studies have shown that lncRNA can regulate physiological processes such as cell differentiation,immune response and apoptosis.LncRNA plays an important role in the occurrence and development of a variety of metabolic diseases and cancers.In the above physiological or pathological processes,lncRNA usually acts as a regulator of gene expression and causes the abnormal expression of downstream target genes.However,how the differential expression of lncRNA itself is regulated in these diseases remains unclear.Like other genes,lncRNA expression is regulated at the DNA level,transcriptional level and post-transcriptional level.The regulation of DNA level is the most important link in gene expression regulation.Studies have shown that the loss of chromosome 8 fragment and DNA copy number variation are common gene events in tumors.LncRNA genes are included in these DNA fragments with deletion or abnormal increase in copy number;In addition to DNA fragment loss and copy number variation,promoter region methylation,histone modification and DNA spatial conformation change are also included.At the transcriptional level,binding and activation of promoters by transcription factors is the most common mechanism.Post-transcriptional regulation mainly refers to the regulation of the stability of lncRNAs.Studies have found that microRNA(miRNA) can bind to the untranslated region(UTR) of the 3′ UTR end of lncRNAs to reduce the level of lncRNAs.In addition,the m^(6)A methylation modification of lncRNAs also affects the stability and function of lncRNAs.In this paper,the regulatory mechanisms of pre-transcriptional level,transcriptional level and post-transcriptional level would be elaborated in order to provide some reference for the subsequent studies on the regulatory mechanisms of lncRNA.