An evolutionarily biased distribution of miRNA sites toward regulatory genes with high promoter-driven intrinsic transcriptional noise.
An evolutionarily biased distribution of miRNA sites toward regulatory genes with high promoter-driven intrinsic transcriptional noise.
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DOI：
10.1186/1471-2148-14-74
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发表时间：
2014-04-04
影响因子：
3.4
通讯作者：
Sartorelli V
中科院分区：
文献类型：
--
作者：
Zare H;Khodursky A;Sartorelli V
miRNA 是后生动物基因表达的一类主要调节因子。通过靶向同源 mRNA，miRNA 参与调节不同细胞和组织类型中的大多数（如果不是全部）生物过程。为了更好地了解这种调控潜力如何在不同靶基因组之间分配，我们对小鼠基因组中 miRNA 靶位点的分布进行了详细、系统的分析。我们使用从 TargetScan 网站下载的 18440 个基因的 3' UTR 中 779 个 miRNA 的预测保守和非保守位点。我们的分析表明，编码调节蛋白的基因的 3' UTR 比非调节、管家和结构基因的 3' UTR 拥有更多数量的 miRNA 位点。对其他 10 个物种中直系同源 3'UTR 的 miRNA 位点的分析表明，调节基因维持或积累了 miRNA 位点，而非调节基因在进化过程中逐渐脱落它们。此外，我们观察到，与低转录噪声的基因相比，由启动子序列内容驱动的具有较高基因表达变异性的基因的 3'UTR 被更多不同的 miRNA 靶向。根据我们的结果，我们设想了一个模型，我们将其称为“选择性包含”，其中具有低转录噪声和稳定表达谱的非调控基因失去了它们的位点，而承受较高转录噪声的调控基因保留并获得了新的位点。这种适应符合需要严格控制调节基因以获得精确和最佳蛋白质水平以正常发挥作用的要求。
miRNAs are a major class of regulators of gene expression in metazoans. By targeting cognate mRNAs, miRNAs are involved in regulating most, if not all, biological processes in different cell and tissue types. To better understand how this regulatory potential is allocated among different target gene sets, we carried out a detailed and systematic analysis of miRNA target sites distribution in the mouse genome. We used predicted conserved and non-conserved sites for 779 miRNAs in 3′ UTR of 18440 genes downloaded from TargetScan website. Our analysis reveals that 3′ UTRs of genes encoding regulatory proteins harbor significantly greater number of miRNA sites than those of non-regulatory, housekeeping and structural, genes. Analysis of miRNA sites for orthologous 3′UTR’s in 10 other species indicates that the regulatory genes were maintaining or accruing miRNA sites while non-regulatory genes gradually shed them in the course of evolution. Furthermore, we observed that 3′ UTR of genes with higher gene expression variability driven by their promoter sequence content are targeted by many more distinct miRNAs compared to genes with low transcriptional noise. Based on our results we envision a model, which we dubbed “selective inclusion”, whereby non-regulatory genes with low transcription noise and stable expression profile lost their sites, while regulatory genes which endure higher transcription noise retained and gained new sites. This adaptation is consistent with the requirements that regulatory genes need to be tightly controlled in order to have precise and optimum protein level to properly function.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
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56.9
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64.5
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通讯作者：
Burge, CB
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4.3
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通讯作者：
Noble WS
影响因子：
4.4
作者：
Cheng C;Bhardwaj N;Gerstein M
通讯作者：
Gerstein M