microRNA与靶基因相互调控机制的研究进展  

Advances in reciprocal regulation mechanisms of microRNAs and target genes

作　　者：赵健志 李欢欢 刘柯欣 林嘉杰 孙绍光[1] Jianzhi Zhao;Huanhuan Li;Kexin Liu;Jiajie Lin;Shaoguang Sun(Cardiovascular Medicine Research Center,Department of Biochemistry and Molecular Biology,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学生物化学与分子生物学教研室,心血管医学研究中心,石家庄050017

出　　处：《科学通报》2021年第24期3123-3140,共18页Chinese Science Bulletin

基　　金：国家自然科学基金(81670273);河北省自然科学基金(H2019206150)资助。

摘　　要：microRNA(miRNA)是一类由内源基因编码的长度约22个核苷酸的单链非编码RNA分子,其通过剪切信使RNA或非编码RNA、沉默或激活转录、primary mi RNA(pri-miRNA)加工及mRNA翻译,调控几乎所有细胞增殖分化、个体生长发育及内环境稳态.大量研究已对miRNA的生物发生和调控机制进行了清晰阐述.然而,关于miRNA的转换机制,尤其是miRNA在特定条件下的快速变化,仍尚未解决.近年来研究发现,靶基因能以序列依赖性方式调控miRNA的生成和降解,表明miRNA和靶基因之间的调控不是单向的,而是相互调控.本文详细概述靶基因调控miRNA的最新进展,归纳二者相互作用的条件和机制,提出miRNA转换的研究方向,以期为深入研究机体内miRNA与靶基因的相互作用及开发miRNA靶向治疗药物提供理论基础.Micro RNAs(mi RNAs), which are encoded by endogenous genes, are a class of single-stranded non-coding RNAs with approximately 22 nt in length. They act on target genes by binding to Argonaute(AGO) family proteins to form mi RNAinduced silencing complexes(miRISCs), thereby functioning at the transcriptional and post-transcriptional levels. With the in-depth study of mi RNAs, it has been found that in addition to messenger RNAs(mRNAs), non-coding RNAs(nc RNAs),primary mi RNAs(pri-mi RNAs), and DNAs can also act as the target genes of mi RNAs. By m RNA or nc RNA cleavage,DNA transcription silence or activation, pri-mi RNA processing, and m RNA translation, mi RNAs regulate almost all cell proliferation/differentiation, individual growth/development, and homeostasis. Since mi RNAs are differentially expressed in various cell types and play a role in the whole development process, studies on mi RNAs have focused on their origins,biogenesis, and mechanisms. However, the mechanisms of mi RNA transformation, especially the rapid change of mi RNAs under specific conditions, have not been well addressed. Recently, it has been discovered that target genes can regulate the biogenesis, degradation, and protection of mi RNAs in a sequence-dependent manner, indicating that the regulation of mi RNAs and target genes is not unidirectional, but reciprocal. The target genes modulate the biogenesis of mi RNAs by mediating the processing, stability, and nuclear export of pri-mi RNAs or precursor mi RNAs(pre-mi RNAs). The modulation depends on the binding of mi RNAs to the complementary sequence on the target genes. However, no general binding pattern represents the modulation of target genes on mi RNA biogenesis. Extensive complementarity between target genes and mi RNAs is a crucial requirement for the target-directed mi RNA degradation(TDMD). Central bulge with varied length is a mismatched region in the center of an extensive complementarity and is essential to trigger TDMD. The mechanisms of TDMD are controversial. It may be due

关 键 词：MICRORNA 靶基因诱导的miRNA降解 拖尾 修剪 靶基因介导的miRNA保护 

分 类 号：Q522[生物学—生物化学]