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Nucleic Acids Research 2005 33(15):4874-4881; doi:10.1093/nar/gki809
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Published online 8 September 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

Human vault-associated non-coding RNAs bind to mitoxantrone, a chemotherapeutic compound

Subash C. B. Gopinath, Akimasa Matsugami1, Masato Katahira1,2,3 and Penmetcha K. R. Kumar*

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 1Supramolecular Biology, International Graduate School of Arts and Sciences, Yokohama City University 1-7-29 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan 2Genome Science Center, RIKEN 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan 3PRESTO, JST Japan

*To whom correspondence should be addressed. Tel: +81 298 61 6085; Fax: +81 298 61 6095; Email: pkr-kumar{at}aist.go.jp

Received July 13, 2005. Revised August 16, 2005. Accepted August 16, 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.


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