Assessing the functional association of intronic miRNAs with their host genes.
Assessing the functional association of intronic miRNAs with their host genes.
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DOI：
10.1261/rna.064386.117
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Margalit H
中科院分区：
文献类型：
--
作者：
Steiman-Shimony A;Shtrikman O;Margalit H
在人类中，近一半的已知microRNA（miRNAs）编码在蛋白质编码基因的内含子内。这些miRNA基因嵌入蛋白质编码基因的序列中暗示了内含子miRNA与其宿主基因之间可能的功能关系。几项使用预测靶点的研究表明，内含子miRNA以拮抗或协同方式影响其宿主的功能。miRNA表达模式和靶点的新实验数据使我们能够通过依赖于实际数据而不是预测来探索这种假定的关联。在这里，我们基于现有实验数据的分析表明，内含子miRNA与其宿主基因之间的潜在功能关联是有限的。对于检测到功能关联的宿主-miRNA实例，其通过自身调节、miRNA和宿主基因的共同靶标或通过靶向参与宿主基因所涉及的途径的转录物来表现。这种功能关联的低发生率与我们观察到的许多内含子miRNA具有独立的转录起始位点并且不与宿主基因共表达一致。然而，与其他内含子miRNAs相比，确实显示出与其宿主的功能关联的内含子miRNAs被发现在进化上更保守。这可能表明，当这种结构具有功能性后果时，有选择性的压力来维持这种结构。
In human, nearly half of the known microRNAs (miRNAs) are encoded within the introns of protein-coding genes. The embedment of these miRNA genes within the sequences of protein-coding genes alludes to a possible functional relationship between intronic miRNAs and their hosting genes. Several studies, using predicted targets, suggested that intronic miRNAs influence their hosts’ function either antagonistically or synergistically. New experimental data of miRNA expression patterns and targets enable exploring this putative association by relying on actual data rather than on predictions. Here, our analysis based on currently available experimental data implies that the potential functional association between intronic miRNAs and their hosting genes is limited. For host-miRNA examples where functional associations were detected, it was manifested by either autoregulation, common targets of the miRNA and hosting gene, or through the targeting of transcripts participating in pathways in which the host gene is involved. This low prevalence of functional association is consistent with our observation that many intronic miRNAs have independent transcription start sites and are not coexpressed with the hosting gene. Yet, the intronic miRNAs that do show functional association with their hosts were found to be more evolutionarily conserved compared to other intronic miRNAs. This might suggest a selective pressure to maintain this architecture when it has a functional consequence.
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