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The architecture of Tetrahymena telomerase holoenzyme

Author

Listed:
  • Jiansen Jiang

    (Immunology and Molecular Genetics, University of California
    University of California
    California Nanosystems Institute, University of California)

  • Edward J. Miracco

    (University of California)

  • Kyungah Hong

    (University of California)

  • Barbara Eckert

    (University of California)

  • Henry Chan

    (University of California)

  • Darian D. Cash

    (University of California)

  • Bosun Min

    (University of California)

  • Z. Hong Zhou

    (Immunology and Molecular Genetics, University of California
    California Nanosystems Institute, University of California)

  • Kathleen Collins

    (University of California)

  • Juli Feigon

    (University of California
    California Nanosystems Institute, University of California)

Abstract

Telomerase adds telomeric repeats to chromosome ends using an internal RNA template and a specialized telomerase reverse transcriptase (TERT), thereby maintaining genome integrity. Little is known about the physical relationships among protein and RNA subunits within a biologically functional holoenzyme. Here we describe the architecture of Tetrahymena thermophila telomerase holoenzyme determined by electron microscopy. Six of the seven proteins and the TERT-binding regions of telomerase RNA (TER) have been localized by affinity labelling. Fitting with high-resolution structures reveals the organization of TERT, TER and p65 in the ribonucleoprotein (RNP) catalytic core. p50 has an unanticipated role as a hub between the RNP catalytic core, p75–p19–p45 subcomplex, and the DNA-binding Teb1. A complete in vitro holoenzyme reconstitution assigns function to these interactions in processive telomeric repeat synthesis. These studies provide the first view of the extensive network of subunit associations necessary for telomerase holoenzyme assembly and physiological function.

Suggested Citation

  • Jiansen Jiang & Edward J. Miracco & Kyungah Hong & Barbara Eckert & Henry Chan & Darian D. Cash & Bosun Min & Z. Hong Zhou & Kathleen Collins & Juli Feigon, 2013. "The architecture of Tetrahymena telomerase holoenzyme," Nature, Nature, vol. 496(7444), pages 187-192, April.
    • Handle: RePEc:nat:nature:v:496:y:2013:i:7444:d:10.1038_nature12062
    DOI: 10.1038/nature12062
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