Gopinath Subash C B, Matsugami Akimasa, Katahira Masato, Kumar Penmetcha K R
Functional Nucleic Acids Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology 1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Nucleic Acids Res. 2005 Sep 8;33(15):4874-81. doi: 10.1093/nar/gki809. Print 2005.
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.
穹窿体是最大的细胞质核糖核蛋白，在癌细胞中过表达。据报道，穹窿体在耐药细胞的细胞核中发挥排出外源性物质的功能，但外源性物质与穹窿体相关蛋白或非编码RNA的相互作用从未被直接观察到。在本研究中，我们发现穹窿体RNA（vRNA），特别是hvg-1和hvg-2 RNA，能与化疗化合物米托蒽醌结合。使用在线探针分析（RNA连接的自发酯交换反应），我们确定了vRNA内的米托蒽醌结合区域。此外，我们利用体外翻译抑制分析，分析了细胞环境中vRNA与米托蒽醌之间的相互作用。综上所述，我们的结果清楚地表明，vRNA有能力结合某些化疗化合物，并且这些相互作用可能通过参与有毒化合物的排出，在穹窿体功能中发挥重要作用。
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