The telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle

Vaults and telomerase are ribonucleoprotein (RNP) particles that share a co mmon protein subunit, TEP1. Although its role in either complex has not yet been defined, TEP1 has been shown to interact with the mouse telomerase RN A and with several of the human vault RNAs in a yeast three-hybrid assay. A n mTep1(-/-)mouse was previously generated which resulted in no apparent ch ange in telomere length or telomerase activity in six generations of mTep1- deficient mice. Here we show that the levels of the telomerase RNA and its association with the telomerase RNP are also unaffected in mTep1(-/-) mice. Although vaults purified from the livers of mTep1(-/-) mice appear structu rally intact by both negative stain and cryoelectron microscopy,three-dimen sional reconstruction of the mTep1(-/-) vault revealed less density in the cap than previously observed for the intact rat vault. Furthermore, the abs ence of TEP1 completely disrupted the stable association of the vault RNA w ith the purified vault particle and also resulted in a decrease in the leve ls and stability of the vault RNA. Therefore, we have uncovered a novel rol e for TEP1 in vivo as an integral vault protein important for the stabiliza tion and recruitment of the vault RNA to the vault particle.