The function of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku

Nat Genet. 2001 Jan;27(1):64-7. doi: 10.1038/83778.

Abstract

The telomerase enzyme lengthens telomeres, an activity essential for chromosome stability in most eukaryotes. The enzyme is composed of a specialized reverse transcriptase and a template RNA. In Saccharomyces cerevisiae, overexpression of TLC1, the telomerase RNA gene, disrupts telomeric structure. The result is both shortened telomere length and loss of a special chromatin structure that normally silences telomere-proximal genes. Because telomerase function is not required for telomeric silencing, we postulated that the dominant-negative effect caused by overexpression of TLC1 RNA originates in a normal interaction between the RNA and an unknown telomeric factor important for silencing; the overexpressed RNA presumably continues to bind the factor and compromises its function. Here we show that a 48-nt stem-loop structure within the 1.3-kb TLC1 RNA is necessary and sufficient for disrupting telomeric silencing and shortening telomeres. Moreover, this short RNA sequence appears to function through an interaction with the conserved DNA end-binding protein Ku. We propose that, in addition to its roles in telomeric silencing, homologous recombination and non-homologous end-joining (NHEJ), S. cerevisiae Ku also helps to recruit or activate telomerase at the telomere through an interaction with this stem-loop of TLC1 RNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Nuclear*
  • Base Pairing
  • Chromosomes, Fungal / genetics
  • Chromosomes, Fungal / metabolism
  • DNA Helicases*
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • Gene Silencing
  • Ku Autoantigen
  • Mutation / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleic Acid Conformation*
  • Phenotype
  • RNA, Catalytic / chemistry*
  • RNA, Catalytic / genetics
  • RNA, Catalytic / metabolism*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction
  • Telomerase / genetics*
  • Telomerase / metabolism
  • Telomere / genetics
  • Telomere / metabolism

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Catalytic
  • Saccharomyces cerevisiae Proteins
  • high affinity DNA-binding factor, S cerevisiae
  • Telomerase
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen