Human vault-associated non-coding RNAs bind to mitoxantrone, a chemotherapeutic compound
Human vault-associated non-coding RNAs bind to mitoxantrone, a chemotherapeutic compound
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DOI：
10.1093/nar/gki809
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发表时间：
2005-01-01
影响因子：
14.9
通讯作者：
Kumar, PKR
中科院分区：
文献类型：
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作者：
Gopinath, SCB;Matsugami, A;Kumar, PKR
人穹窿是最大的胞质核糖核蛋白，在癌细胞中过表达。据报道，拱顶在从抗性细胞的细胞核中挤出外源性物质中起作用，但外源性物质与拱顶相关蛋白或非编码RNA的相互作用从未被直接观察到。在本研究中，我们发现穹窿RNA（vRNA），特别是hvg-1和hvg-2 RNA，与化疗化合物米托蒽醌结合。使用在线探测测定（RNA键的自发酯交换），我们已经确定了vRNA内的米托蒽醌结合区域。此外，我们分析了vRNA和米托蒽醌在细胞环境中的相互作用，使用体外翻译抑制试验。总之，我们的结果清楚地表明，vRNA具有结合某些化疗化合物的能力，这些相互作用可能通过参与有毒化合物的输出在穹窿功能中发挥重要作用。
Human vaults are the largest cytoplasmic ribonucleoprotein and are overexpressed in cancer cells. Vaults reportedly function in the extrusion of xenobiotics from the nuclei of resistant cells, but the interactions of xenobiotics with the vault-associated proteins or non-coding RNAs have never been directly observed. In the present study, we show that vault RNAs (vRNAs), specifically the hvg-1 and hvg-2 RNAs, bind to a chemotherapeutic compound, mitoxantrone. Using an in-line probing assay (spontaneous transesterification of RNA linkages), we have identified the mitoxantrone binding region within the vRNAs. In addition, we analyzed the interactions between vRNAs and mitoxantrone in the cellular milieu, using an in vitro translation inhibition assay. Taken together, our results clearly suggest that vRNAs have the ability to bind certain chemotherapeutic compounds and these interactions may play an important role in vault function, by participating in the export of toxic compounds.