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    Nucleic Acids Res. 2005 Sep 8;33(15):4874-81. Print 2005.

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

    Gopinath SC, Matsugami A, Katahira M, Kumar PK.

    Source

    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.

    Abstract

    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.

    PMID:
    16150923
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC1201340
    Free PMC Article

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