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RNA binding proteins (RBPs) regulate lncRNA nuclear retention

机译:RNA结合蛋白(RBPS)调节LNCRNA核保留

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It is well known that functional modes of lncRNAs are intimately associated with their subcellular localization1 and relative nuclear enrichment of lncRNAs compared to mRNAs is a prevalent phenomenon2. As RBPs control the production, maturation, localization, translation, and degradation of cellular RNAs3, we reason that it is important to uncover partner RBPs that can bind and facilitate lncRNA nuclear localization. In this study, we thus harnessed the recently released large scale of eCLIP data4 and subcellular RNA-seq data5 available in K562 and HepG2 cell lines to characterize lncRNA-RBP interactome and uncovered potential factors and associated mechanisms determining lncRNA nuclear retention. Analyses of the subcellular RNA-seq data identified nuclear enriched lncRNAs (nuc-lncRNAs) and confirmed that lncRNAs and eRNAs (enhancer associated lncRNAs) are relatively nuclear enriched in both cells. By integrating the RBP binding profiles, we next generated RBP/nuc-lncRNA interaction map to identify RBPs associated with nuc-lncRNAs including HNRNPU, SAFB2, KHSRP and KHDRBS1 in K562 and HRNPNPC as well as HNRNPL in HepG2 cell lines. To further confirm the above findings, HNRNPU was knocked down and which led to nuclear retention of a panel of lncRNAs.
机译:众所周知,LNCRNA的功能模式与其亚细胞定位密切相关 1 与MRNA相比,LNCRNA的相对核富集是一种普遍存存的现象 2 。随着RBP控制细胞RNA的生产,成熟,定位,翻译和降解 3 ,我们认为揭示可以结合和促进LNCRNA核定定位的伴侣RBP非常重要。在这项研究中,我们利用最近发布了大规模的Eclip数据 4 和亚细胞RNA-SEQ数据 5 可用于K562和HepG2细胞系,以表征LNCRNA-RBP蛋白酶和未覆盖的潜在因素和相关机制,确定LNCRNA核保留。亚细胞RNA-SEQ数据鉴定的核富集的LNCRNA(NUC-LNCRNA)分析并证实了LNCRNA和ERNAS(增强子相关的LNCRNA)在两种细胞中富集。通过集成RBP结合谱,我们下次产生的RBP / NUC-LNCRNA相互作用图,以鉴定与NUC-LNCRNA相关联的RBP,包括HNRNPU,SAFB2,KHSRP和KHDRBS1,在K562和HRNPNPC中以及HEPG2细胞系中的HNRNPL。为了进一步证实上述研究结果,HNRNPU被击倒,导致核保留LNCRNA面板。

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