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  • The EMBO Journal (2006) 25, 3156 - 3166
  • doi:10.1038/sj.emboj.7601195

Published online: 15 June 2006

Structure of stem-loop IV of Tetrahymena telomerase RNA

Yu Chen1, Jessica Fender1, Jason D Legassie2, Michael B Jarstfer2, Tracy M Bryan3 and Gabriele Varani1,4

  1. Department of Chemistry, University of Washington, Seattle WA, USA
  2. Division of Medicinal Chemistry and Natural Products, University of North Carolina, Chapel Hill, NC, USA
  3. Children's Medical Research Institute, Westmead, NSW, Australia
  4. Department of Biochemistry, University of Washington, Seattle WA, USA

Correspondence to:

Gabriele Varani, Departments of Chemistry & Biochemistry, University of Washington, Box 351700, Seattle, WA 98185-1700, USA. Tel: +1 206 543 7113; Fax: +1 206 685 8665; E-mail: varani@chem.washington.edu

Received 12 January 2006; Accepted 15 May 2006

Conserved domains within the RNA component of telomerase provide the template for reverse transcription, recruit protein components to the holoenzyme and are required for enzymatic activity. Among the functionally essential domains in ciliate telomerase RNA is stem-loop IV, which strongly stimulates telomerase activity and processivity even when provided in trans. The NMR structure of Tetrahymena thermophila stem-loop IV shows a highly structured distal stem-loop linked to a conformationally flexible template-proximal region by a bulge that severely kinks the entire RNA. Through extensive structure–function studies, we identify residues that contribute to both these structural features and to enzymatic activity, with no apparent effect on the binding of TERT protein. We propose that the bending induced by the GA bulge and the flexibility of the template-proximal region allow positioning of the prestructured apical loop during the catalytic cycle.

  • Keywords:

    • NMR,
    • RNA structure,
    • ribonucleoprotein,
    • stem-loop,
    • telomerase