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

Nucleic Acids Res. 2001 Feb 1;29(3):598-603. doi: 10.1093/nar/29.3.598.

Abstract

Telomerase is a ribonucleoprotein (RNP) particle required for the replication of telomeres. The RNA component, termed hTR, of human telomerase contains a domain structurally and functionally related to box H/ACA small nucleolar 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 hTR with H/ACA snoRNP core proteins, we have attempted to express hTR in a genetically tractable system, Saccharomyces cerevisiae. Both mature non-polyadenylated and polyadenylated forms of hTR accumulate in yeast. The former is associated with all yeast H/ACA snoRNP core proteins, unlike TLC1 RNA, the endogenous RNA component of yeast telomerase. We show that the presence of the H/ACA snoRNP proteins Cbf5p, Nhp2p and Nop10p, but not Gar1p, is required 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 proteins. Our results demonstrate that yeast telomerase is unrelated to H/ACA snoRNPs. In addition, they show that the accumulation in yeast of the mature RNA component of human telomerase depends on its association with three of the four core H/ACA snoRNP proteins. It is likely that this is the case in human cells as well.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Recombinant
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Enzymologic
  • Genetic Vectors / genetics
  • Humans
  • Hydro-Lyases*
  • Microtubule-Associated Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Poly A / genetics
  • Protein Binding
  • RNA / genetics
  • RNA / metabolism*
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins, Small Nuclear / metabolism*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Telomerase / genetics*

Substances

  • DNA, Recombinant
  • Fungal Proteins
  • Microtubule-Associated Proteins
  • NOP10 protein, S cerevisiae
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear
  • Saccharomyces cerevisiae Proteins
  • NHP2 protein, S cerevisiae
  • Poly A
  • RNA
  • Telomerase
  • Hydro-Lyases
  • CBF5 protein, S cerevisiae