Mass Spectrometry-Based Proteomics Approach Characterizes the Dual Functionality of miR-328 in Monocytes
Mass Spectrometry-Based Proteomics Approach Characterizes the Dual Functionality of miR-328 in Monocytes
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DOI：
10.3389/fphar.2019.00640
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发表时间：
2019-06-05
影响因子：
5.6
通讯作者：
Jakobsson, Per Johan
中科院分区：
文献类型：
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作者：
Saul, Meike J.;Hegewald, Anett B.;Jakobsson, Per Johan
MicroRNA (miR) 是一种小型非编码 RNA，通过翻译抑制或 RNA 降解（称为经典 miR 功能）来控制靶基因的表达。最近发现 miR-328 具有非常规功能，可以通过拮抗异源核糖核蛋白 E2 (hnRNP E2) 的活性来激活基因表达，这开辟了一个未经探索且令人兴奋的基因表达调控领域。这种非典型 miR 功能的全球重要性尚不清楚。为了更好地了解新的 miR 活性，我们在分化的 MonoMac6 (MM6) 细胞中进行了基于区室特异性串联质量标签 (TMT) 的蛋白质组分析，以监测 miR-328 敲低引起的基因表达变化。我们鉴定了一系列新的潜在 miR-328/hnRNP E2 和 miR-328 靶标，这些靶标参与调节区室特异性细胞过程，例如炎症或 RNA 剪接。这项研究首次揭示了非典型 miR 功能的全球意义。
MicroRNAs (miRs) are small noncoding RNAs which control the expression of target genes by either translational repression or RNA degradation, known as canonical miR functions. The recent discovery that miR-328 has a noncanonical function and can activate gene expression by antagonizing the activity of heterogeneous ribonuclear protein E2 (hnRNP E2) opens an unexplored and exciting field of gene expression regulation. The global importance of such noncanonical miR function is not yet known. In order to achieve a better understanding of the new miR activity, we performed a compartment specific tandem mass tag (TMT)-based proteomic analysis in differentiated MonoMac6 (MM6) cells, to monitor gene expression variations in response to miR-328 knockdown. We identified a broad spectrum of novel potential miR-328/hnRNP E2 and miR-328 targets involved in regulation of compartment specific cellular processes, such as inflammation or RNA splicing. This study provides first insights of the global significance of noncanonical miR function.