Multiple human vault RNAs - Expression and association with the vault complex

Human vaults are intracellular ribonucleoprotein particles believed to be i nvolved in multidrug resistance. The complex consists of a major vault prot ein (MVP), two minor vault proteins (VPARP and TEP1), and several small unt ranslated RNA molecules. Three human vault RNA genes (HVG1-3) have been des cribed, and a fourth was found in a homology search (HVG4). In the literatu re only the association of hvg1 with vaults was shown in vivo. However, in a yeast three-hybrid screen the association of hvg1, hvg2, and hvg4 with TE P1 was demonstrated. In this study we investigated the expression and vault association of different vault RNAs in a variety of cell lines, including pairs of drug-sensitive and drug-resistant cells. HVG1-3 are expressed in a ll cell lines examined, however, none of the cell lines expressed HVG4. Thi s probably is a consequence of the absence of essential external polymerase III promoter elements. The bulk of the vault RNA associated with vaults wa s hvg1. Interestingly, an increased amount of hvg3 was bound to vaults isol ated from multidrug-resistant cell lines. Our findings suggest that vaults bind the RNA molecules with different affinities in different situations. T he ratio in which the vault RNAs are associated with vaults might be of fun ctional importance.