Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction
Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction
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DOI：
10.15252/embj.201798441
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发表时间：
2019-09-02
期刊：
影响因子：
11.4
通讯作者：
Takahashi, Takashi
中科院分区：
文献类型：
--
作者：
Kajino, Taisuke;Shimamura, Teppei;Takahashi, Takashi
长非编码RNA(LncRNAs)通过不同的机制在广泛的过程中发挥作用，尽管它们在癌基因和/或肿瘤抑制因子的调控中的作用仍然很难捉摸。我们使用K超级计算机和基于局部距离相关性的Gimlet算法，使用基于系统生物学的方法，对影响MYC活性的lncRNAs进行了全局搜索。因此，MYMLR被鉴定并实验表明，尽管表达水平较低，但仍能维持MYC的转录活性和细胞周期进展。对MYMLR结合蛋白的蛋白质组学搜索发现了PCBP2，同时也发现MYMLR在MYC启动子附近与PCBP2合作放置了一个557kb的上游增强子区。这些发现暗示了MYMLR在典型癌基因MYC的调控中的关键作用，并为未来关于低拷贝数的lncRNAs参与调控其他关键癌基因和肿瘤抑制基因的研究奠定了基础。
Long non-coding RNAs (lncRNAs) function in a wide range of processes by diverse mechanisms, though their roles in regulation of oncogenes and/or tumor suppressors remain rather elusive. We performed a global search for lncRNAs affecting MYC activity using a systems biology-based approach with a K supercomputer and the GIMLET algorism based on local distance correlations. Consequently, MYMLR was identified and experimentally shown to maintain MYC transcriptional activity and cell cycle progression despite the low levels of expression. A proteomic search for MYMLR-binding proteins identified PCBP2, while it was also found that MYMLR places a 557-kb upstream enhancer region in the proximity of the MYC promoter in cooperation with PCBP2. These findings implicate a crucial role for MYMLR in regulation of the archetypical oncogene MYC and warrant future studies regarding the involvement of low copy number lncRNAs in regulation of other crucial oncogenes and tumor suppressor genes.