Pyrimidine motif triple helix in the Kluyveromyces lactis telomerase RNA pseudoknot is essential for function in vivo

Darian D. Cash, Osnat Cohen-Zontag, Nak Kyoon Kim, Kinneret Shefer, Yogev Brown, Nikolai B. Ulyanov, Yehuda Tzfati*, Juli Feigon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Telomerase is a ribonucleoprotein complex that extends the 3′ ends of linear chromosomes. The specialized telomerase reverse transcriptase requires a multidomain RNA (telomerase RNA, TER), which includes an integral RNA template and functionally important template-adjacent pseudoknot. The structure of the human TER pseudoknot revealed that the loops interact with the stems to form a triple helix shown to be important for activity in vitro. A similar triple helix has been predicted to form in diverse fungi TER pseudoknots. The solution NMR structure of the Kluyveromyces lactis pseudoknot, presented here, reveals that it contains a long pyrimidine motif triple helix with unexpected features that include three individual bulge nucleotides and a C+•G-C triple adjacent to a stem 2-loop 2 junction. Despite significant differences in sequence and base triples, the 3D shape of the human and K. lactis TER pseudo-knots are remarkably similar. Analysis of the effects of nucleotide substitutions on cell growth and telomere lengths provides evidence that this conserved structure forms in endogenously assembled telomerase and is essential for telomerase function in vivo.

Original languageAmerican English
Pages (from-to)10970-10975
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number27
DOIs
StatePublished - 2 Jul 2013

Keywords

  • Hoogsteen
  • RNA structure
  • RNA triplex
  • Yeast

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