Stable expression in yeast of the mature form of human telomerase RNA depends on its association with the box H/ACA small nucleolar RNP proteins Cbf5p, Nhp2p and Nop10p

Telomerase is a ribonucleoprotein (RNP) particle required for the replicati on of telomeres. The RNA component, termed hTR, of human telomerase contain s a domain structurally and functionally related to box H/ACA small nucleol ar RNAs (snoRNAs). Furthermore, hTR is known to be associated with two core components of H/ACA snoRNPs, hGar1p and Dyskerin (the human counterpart of yeast Cbf5p). To assess the functional importance of the association of hT R with H/ACA snoRNP core proteins, we have attempted to express hTR in a ge netically tractable system, Saccharomyces cerevisiae. Both mature non-polya denylated and polyadenylated forms of hTR accumulate in yeast. The former i s associated with all yeast H/ACA snoRNP core proteins, unlike TLC1 RNA, th e endogenous RNA component of yeast telomerase. We show that the presence o f the H/ACA snoRNP proteins Cbf5p, Nhp2p and Nop10p, but not Gar1p, is requ ired for the accumulation of mature non-polyadenylated hTR in yeast, while accumulation of TLC1 RNA is not affected by the absence of any of these pro teins. Our results demonstrate that yeast telomerase is unrelated to H/ACA snoRNPs. In addition, they show that the accumulation in yeast of the matur e RNA component of human telomerase depends on its association with three o f the four core H/ACA snoRNP proteins. It is likely that this is the case i n human cells as well.