A novel pseudoknot element is essential for the action of a yeast telomerase

Yehuda Tzfati, Zachary Knight, Jagoree Roy, Elizabeth H. Blackburn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Telomerase contains an essential RNA, which includes the template sequence copied by the reverse transcription action of telomerase into telomeric DNA. Using phylogenetic comparison, we identified seven conserved sequences in telomerase RNAs from Kluyveromyces budding yeasts. We show that two of these sequences, CS3 and CS4, are essential for normal telomerase function and can base-pair to form a putative long-range pseudoknot. Disrupting this base-pairing was deleterious to cell growth, telomere maintenance, and telomerase activity. Restoration of the base-pairing potential alleviated these phenotypes. Mutating this pseudoknot caused a novel mode of shifting of the boundaries of the RNA template sequence copied by telomerase. A phylogenetically derived model of yeast TER structure indicates that these RNAs can form two alternative predicted core conformations of similar stability: one brings the CS3/CS4 pseudoknot spatially close to the template; in the other, CS3 and CS4 move apart and the conformation of the template is altered. We propose that such disruption of the pseudoknot, and potentially the predicted telomerase RNA conformation, affects polymerization to cause the observed shifts in template usage.

Original languageEnglish
Pages (from-to)1779-1788
Number of pages10
JournalGenes and Development
Volume17
Issue number14
DOIs
StatePublished - 15 Jul 2003
Externally publishedYes

Keywords

  • Telomerase RNA pseudoknot
  • Telomerase RNA secondary structure
  • Telomerase template miscopying
  • Telomerase, yeast telomerase RNA

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