The regulatory impact of RNA-binding proteins on microRNA targeting.

The regulatory impact of RNA-binding proteins on microRNA targeting.
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RNA结合蛋白对microRNA靶向的调节作用。

DOI:
10.1038/s41467-021-25078-5
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发表时间:
2021-08-20
影响因子:
16.6
通讯作者:
Baek D
Baek D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kim S;Kim S;Chang HR;Kim D;Park J;Son N;Park J;Yoon M;Chae G;Kim YK;Kim VN;Kim YK;Nam JW;Shin C;Baek D

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Argonaute是后生动物miRNA靶向(MT)的主要介导者。在目前鉴定的> 1,500种人类RNA结合蛋白(RBP)中,只有少数RBP已知可增强MT,而其他几种据报道可抑制MT,因此RBP对MT的全球影响难以捉摸。在这项研究中,我们系统地分析了150个人类RBPs的全转录组结合位点,并评估了单个RBPs对MT疗效的定量影响。与以前的研究相比,我们发现,大多数RBPs显着影响MT和所有这些MT调节RBPs功能MT增强剂,而不是抑制剂,通过使Argonaute访问的目标网站的本地二级结构。我们的研究结果阐明了人类RBPs对MT的未被重视的调控影响,并且由于这些RBPs可能在由后生动物miRNA控制的基因调控网络中发挥关键作用,因此应该在共调控RBPs的背景下理解MT。miRNA被加载到Argonaute蛋白中并抑制互补mRNA靶标。在这里,作者展示了RNA结合蛋白在有效的miRNA靶向中未被重视的作用,并扩展了目前对miRNA靶向的理解。
Argonaute is the primary mediator of metazoan miRNA targeting (MT). Among the currently identified >1,500 human RNA-binding proteins (RBPs), there are only a handful of RBPs known to enhance MT and several others reported to suppress MT, leaving the global impact of RBPs on MT elusive. In this study, we have systematically analyzed transcriptome-wide binding sites for 150 human RBPs and evaluated the quantitative effect of individual RBPs on MT efficacy. In contrast to previous studies, we show that most RBPs significantly affect MT and that all of those MT-regulating RBPs function as MT enhancers rather than suppressors, by making the local secondary structure of the target site accessible to Argonaute. Our findings illuminate the unappreciated regulatory impact of human RBPs on MT, and as these RBPs may play key roles in the gene regulatory network governed by metazoan miRNAs, MT should be understood in the context of co-regulating RBPs. miRNAs are loaded into Argonaute protein and repress complementary mRNA targets. Here the authors show the unappreciated role of RNA binding proteins for efficient miRNA targeting and expand the current understanding of miRNA targeting.
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