miRNA与其靶mRNA的相互作用:绑定位点的质量与数量特征的整合计算分析(英文)  

Computational Analysis of miRNA and Target mRNA Interactions:Combined Effects of The Quantity and Quality of Their Binding Sites

作　　者：付聪[1] 林魁[1] 

机构地区：[1]北京师范大学生命科学学院,北京100875

出　　处：《生物化学与生物物理进展》2009年第5期608-615,共8页Progress In Biochemistry and Biophysics

基　　金：supported by a grant from The National Natural Science Foundation of China(30571037,30770445)~~

摘　　要：miRNAs通过完全或不完全的碱基互补绑定到信使RNA(mRNA)上,通过抑制翻译或者直接导致mRNA降解的方式来调节靶基因的表达.为了研究miRNAs在转录水平上面的调控作用,两种人类基因组中组织特异的miRNAs(miR-1和miR-124)被转染到HeLa细胞中,微阵列(microarray)分析转染前后细胞中各基因mRNA表达水平变化情况的结果表明:动物基因组中靶基因与miRNAs不完全的碱基互补也会导致mRNA的直接降解.通过分析实验得到的mRNA表达水平变化数据,发现这相同miRNA的不同靶基因mRNA表达水平的下调倍数有着明显的差别,推测这些靶基因mRNA序列本身存在某些影响其受调节程度的因素.为此,提取和分析这些靶基因mRNA的序列特征,通过对这些序列特征与mRNA表达水平下调数据进行统计相关分析,最终发现,miRNA靶基因受调节的程度与以下几个因素相关联:mRNA序列中miRNA靶位点的个数,靶位点与miRNA序列碱基互补的程度,以及绑定后形成二级结构的稳定程度(即最低自由能的大小).在此基础上,初步建立起一个多因子作用下的miRNA靶基因mRNA表达水平下调程度模型,分析表明:该模型在一定程度上可以反映了部分序列特征对于miRNA靶基因mRNA表达水平下调程度的影响.MicroRNAs（miRNAs） act by binding to complementary sites on target messenger RNA（mRNA） to induce mRNA degradation and/or translational repression.To investigate the influence of miRNAs at transcript levels,two human miRNAs（miR-1 and miR-124） were transfected into HeLa cells and microarrays used to examine changes in the mRNA profile showed that many genes were downregulated and that the fold decreases in levels of these target mRNAs differed remarkably.Features depicting interactions between miRNAs and their respective target mRNAs,such as the number of putative binding sites,the strength of complementary matches and the degree of stabilization of the binding duplex,were extracted and analyzed.It was found that,for a given target mRNA,both the quality and quantity of miRNA binding sites significantly affected its degree of destabilization.To delineate these types of interactions,a simple statistical model was proposed,which considers the combined effects of both the quality and quantity of miRNA binding sites on the degradation levels of target mRNAs.The analysis provides insights into how any animal miRNA might interact with its target mRNA.It will help us in designing more accurate methods for predicting miRNA targets and should improve understanding of the origins of miRNAs.

关 键 词：MICRORNA 靶位点 靶mRNA 下调 

分 类 号：Q291[生物学—细胞生物学] Q74