U.O.C. Genetica Medica e di Laboratorio, Ospedale Antonio Cardarelli, 80131 Napoli, Italy.
Dipartimento Scienze della Vita e Sanità Pubblica, Sezione di Biologia Applicata, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Genes (Basel). 2020 Apr 29;11(5):482. doi: 10.3390/genes11050482.
Gene expression regulation is achieved through an intricate network of molecular interactions, in which trans-acting transcription factors (TFs) and small noncoding RNAs (sncRNAs), including microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), play a key role. Recent observations allowed postulating an interplay between TFs and sncRNAs, in that they may possibly share DNA-binding sites. The aim of this study was to analyze the complete subset of miRNA and piRNA sequences stored in the main databases in order to identify the occurrence of conserved motifs and subsequently predict a possible innovative interplay with TFs at a transcriptional level. To this aim, we adopted an original in silico workflow to search motifs and predict interactions within genome-scale regulatory networks. Our results allowed categorizing miRNA and piRNA motifs, with corresponding TFs sharing complementary DNA-binding motifs. The biological interpretation of the gene ontologies of the TFs permitted observing a selective enrichment in developmental pathways, allowing the distribution of miRNA motifs along a topological and chronological frame. In addition, piRNA motifs were categorized for the first time and revealed specific functional implications in somatic tissues. These data might pose experimental hypotheses to be tested in biological models, towards clarifying novel in gene regulatory routes.
基因表达调控是通过复杂的分子相互作用网络实现的，其中反式作用转录因子（TFs）和小非编码 RNA（sncRNA），包括 microRNAs（miRNAs）和 PIWI 相互作用 RNA（piRNAs），发挥着关键作用。最近的观察结果表明，TFs 和 sncRNA 之间可能存在相互作用，因为它们可能共享 DNA 结合位点。本研究的目的是分析主要数据库中存储的完整 miRNA 和 piRNA 序列子集，以识别保守基序的出现，并随后预测在转录水平上与 TFs 可能存在的创新性相互作用。为此，我们采用了一种原始的计算工作流程来搜索基序并预测基因组规模调控网络内的相互作用。我们的结果允许对 miRNA 和 piRNA 基序进行分类，相应的 TF 共享互补的 DNA 结合基序。TFs 的基因本体论的生物学解释允许观察到在发育途径中的选择性富集，允许 miRNA 基序沿着拓扑和时间框架分布。此外，piRNA 基序首次被分类，并揭示了在体细胞组织中的特定功能意义。这些数据可能为实验假说提供依据，以便在生物模型中进行测试，以阐明新的基因调控途径。
