1. Chromosomes and Gene Expression
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Minimized human telomerase maintains telomeres and resolves endogenous roles of H/ACA proteins, TCAB1, and Cajal bodies

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Cite this article as: eLife 2016;5:e18221 doi: 10.7554/eLife.18221

Abstract

We dissected the importance of human telomerase biogenesis and trafficking pathways for telomere maintenance. Biological stability of human telomerase RNA (hTR) relies on H/ACA proteins, but other eukaryotes use other RNP assembly pathways. To investigate additional rationale for human telomerase assembly as H/ACA RNP, we developed a minimized cellular hTR. Remarkably, with only binding sites for telomerase reverse transcriptase (TERT), minimized hTR assembled biologically active enzyme. TERT overexpression was required for cellular interaction with minimized hTR, indicating that H/ACA RNP assembly enhances endogenous hTR-TERT interaction. Telomere maintenance by minimized telomerase was unaffected by elimination of the telomerase holoenzyme Cajal body chaperone TCAB1 or the Cajal body scaffold protein Coilin. Surprisingly, wild-type hTR also maintained and elongated telomeres in TCAB1 or Coilin knockout cells, with distinct changes in telomerase action. Overall we elucidate trafficking requirements for telomerase biogenesis and function and expand mechanisms by which altered telomere maintenance engenders human disease.

Article and author information

Author details

  1. Jacob M Vogan

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  2. Xiaozhu Zhang

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  3. Daniel T Youmans

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  4. Samuel G Regalado

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  5. Joshua Z Johnson

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  6. Dirk Hockemeyer

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  7. Kathleen Collins

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    kcollins@berkeley.edu
    Competing interests
    Kathleen Collins, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3172-7088

Funding

National Heart, Lung, and Blood Institute (RO1 HL079585)

  • Jacob M Vogan
  • Xiaozhu Zhang
  • Daniel T Youmans
  • Kathleen Collins

Ellison Medical Foundation

  • Samuel G Regalado
  • Joshua Z Johnson
  • Dirk Hockemeyer

Glenn Foundation for Medical Research

  • Samuel G Regalado
  • Joshua Z Johnson
  • Dirk Hockemeyer

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Carol Greider, Johns Hopkins University, United States

Publication history

  1. Received: May 26, 2016
  2. Accepted: August 14, 2016
  3. Accepted Manuscript published: August 15, 2016 (version 1)
  4. Version of Record published: August 30, 2016 (version 2)

Copyright

© 2016, Vogan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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