Long noncoding RNA HOTAIR interacts with Y-Box Protein-1 (YBX1) to regulate cell proliferation.

Long noncoding RNA HOTAIR interacts with Y-Box Protein-1 (YBX1) to regulate cell proliferation.
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长非编码 RNA HOTAIR 与 Y-Box Protein-1 (YBX1) 相互作用调节细胞增殖

DOI:
10.26508/lsa.202101139
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发表时间:
2021-09
影响因子:
4.4
通讯作者:
Ge F
Ge F
中科院分区:
生物学2区
文献类型:
--
作者:
Li S;Xiong Q;Chen M;Wang B;Yang X;Yang M;Wang Q;Cui Z;Ge F

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作者确定HOTAIR特异性结合YBX 1并促进其核转位,然后通过刺激PI 3 K/Akt和ERK/RSK信号通路调节细胞增殖。HOTAIR是一种长链非编码RNA(lncRNA),是调节与癌症发展相关的多种过程的重要因子。在这里,我们使用全面鉴定RNA结合蛋白质的质谱(ChIRP-MS),探索HOTAIR蛋白质相互作用组。我们能够识别出348种与HOTAIR相互作用的蛋白质,使我们能够建立一个高度相互关联的HOTAIR-蛋白质相互作用网络。我们进一步开发了一种新的近红外荧光蛋白(iRFP)-三分子荧光互补(TriFC)系统,以评估HOTAIR及其相互作用蛋白之间的相互作用。然后,我们确定HOTAIR特异性结合YBX 1,促进YBX 1核转位,并刺激PI 3 K/Akt和ERK/RSK信号通路。我们进一步证明HOTAIR对细胞增殖的影响,至少部分是通过调节两个YBX 1下游靶点磷酸烯醇丙酮酸羧激酶2(PCK 2)和血小板衍生生长因子受体β来实现的。我们的研究结果揭示了一种新的机制,即lncRNA能够通过改变细胞内蛋白质定位来调节细胞增殖。此外,本文开发的成像工具对于lncRNA-蛋白质相互作用的未来体内成像具有极好的潜力。
The authors determined that HOTAIR specifically bind to YBX1 and promote its nuclear translocation, and then regulating cell proliferation by stimulating the PI3K/Akt and ERK/RSK signaling pathways. HOTAIR is a long noncoding RNA (lncRNA) which serves as an important factor regulating diverse processes linked with cancer development. Here, we used comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) to explore the HOTAIR-protein interactome. We were able to identify 348 proteins interacting with HOTAIR, allowing us to establish a heavily interconnected HOTAIR-protein interaction network. We further developed a novel near-infrared fluorescent protein (iRFP)-trimolecular fluorescence complementation (TriFC) system to assess the interaction between HOTAIR and its interacting proteins. Then, we determined that HOTAIR specifically binds to YBX1, promotes YBX1 nuclear translocation, and stimulates the PI3K/Akt and ERK/RSK signaling pathways. We further demonstrated that HOTAIR exerts its effects on cell proliferation, at least in part, through the regulation of two YBX1 downstream targets phosphoenolpyruvate carboxykinase 2 (PCK2) and platelet derived growth factor receptor β. Our findings revealed a novel mechanism, whereby an lncRNA is able to regulate cell proliferation via altering intracellular protein localization. Moreover, the imaging tools developed herein have excellent potential for future in vivo imaging of lncRNA–protein interaction.
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