We found that UP1, a proteolytic product of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), both enhances and represses the telomerase activity. The formation of the UP1–telomerase RNA–telomeric DNA ternary complex was revealed by a gel retardation experiment. The interactions in the ternary and binary complexes were elucidated by NMR. UP1 has two nucleic acid-binding domains, BD1 and BD2. In the UP1–telomerase RNA binary complex, both BD1 and BD2 interact with telomerase RNA. Interestingly, when telomeric DNA was added to the binary complex, telomeric DNA bound to BD1 in place of telomerase RNA. Thus, BD1 basically binds to telomeric DNA, while BD2 mainly binds to telomerase RNA, which resulted in the formation of the ternary complex. Here, UP1 bridges telomerase and telomeric DNA. It is supposed that UP1/hnRNP A1 serves to recruit telomerase to telomeric DNA through the formation of the ternary complex. A model has been proposed for how hnRNP A1/UP1 contributes to enhancement of the telomerase activity through recruitment and unfolding of the quadruplex of telomeric DNA.

It is supposed that ribonucleoprotein particle vault is involved in detoxification processes and thus is related to multidrug resistance. The vault is composed of three proteins and three vault RNAs, hvg-1, -2 and -3. The direct interactions between vault components and drugs were not reported. Recently, we revealed the interactions between vault RNAs and mitoxantrone. Here, we examined the interactions between hvg-2 and six antitumor drugs by a chemical shift perturbation method of NMR. It was found that in addition to mitoxantrone, hvg-2 can interact with two drugs basically in the same way using the same site. The difference in the affinity was also noticed among three drugs. Hvg-2 did not bind to the other three drugs. It is suggested that the common or closely related chemical structure of the positive three drugs is recognized by vault RNA.