Laboratory of Molecular Modeling and Design, State key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Rd,, Dalian, 116023, PR China.
BMC Genomics. 2012 Dec 18;13:707. doi: 10.1186/1471-2164-13-707.
microRNAs (miRNAs) represent a class of small (typically 22 nucleotides in length) non-coding RNAs that can degrade their target mRNAs or block their translation. Recent research showed that copy number alterations of miRNAs and their target genes are highly prevalent in cancers; however, the evolutionary and biological functions of naturally existing copy number variable miRNAs (CNV-miRNAs) among individuals have not been studied extensively throughout the genome.
In this study, we comprehensively analyzed the properties of genes regulated by CNV-miRNAs, and found that CNV-miRNAs tend to target a higher average number of genes and prefer to synergistically regulate the same genes; further, the targets of CNV-miRNAs tend to have higher variability of expression within and between populations. Finally, we found the targets of CNV-miRNAs are more likely to be differentially expressed among tissues and developmental stages, and participate in a wide range of cellular responses.
Our analyses of CNV-miRNAs provide new insights into the impact of copy number variations on miRNA-mediated post-transcriptional networks. The deeper interpretation of patterns of gene expression variation and the functional characterization of CNV-miRNAs will help to broaden the current understanding of the molecular basis of human phenotypic diversity.
microRNAs (miRNAs) 是一类小的（通常长度为 22 个核苷酸）非编码 RNA，可以降解其靶 mRNAs 或阻止其翻译。最近的研究表明，miRNAs 和其靶基因的拷贝数改变在癌症中非常普遍；然而，个体间自然存在的拷贝数可变 miRNAs (CNV-miRNAs) 的进化和生物学功能尚未在整个基因组中得到广泛研究。
在这项研究中，我们全面分析了受 CNV-miRNAs 调控的基因的特性，发现 CNV-miRNAs 倾向于靶向更高平均数量的基因，并倾向于协同调节相同的基因；此外，CNV-miRNAs 的靶基因在个体内和个体间的表达变异性更高。最后，我们发现 CNV-miRNAs 的靶基因在组织和发育阶段之间的表达差异更大，并且参与广泛的细胞反应。
我们对 CNV-miRNAs 的分析为拷贝数变异对 miRNA 介导的转录后网络的影响提供了新的见解。对基因表达变异模式的更深入解释和 CNV-miRNAs 的功能特征将有助于拓宽对人类表型多样性的分子基础的现有理解。
