Human vault-associated non-coding RNAs bind to mitoxantrone, a chemotherapeutic compound.
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.
Gopinath
Subash C B
SC
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.
Matsugami
Akimasa
A
Katahira
Masato
M
Kumar
Penmetcha K R
PK
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D006801:Humans; D008942:Mitoxantrone / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D022661:RNA, Untranslated / Q000737:chemistry / Q000378:metabolism*; D020394:Vault Ribonucleoprotein Particles / Q000737:chemistry / Q000378:metabolism*
D000970:Antineoplastic Agents; D022661:RNA, Untranslated; D020394:Vault Ribonucleoprotein Particles; D008942:Mitoxantrone