Minimized human telomerase maintains telomeres and resolves endogenous roles of H/ACA proteins, TCAB1, and Cajal bodies
- University of California, Berkeley, United States
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
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.
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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Minimized human telomerase maintains telomeres and resolves endogenous roles of H/ACA proteins, TCAB1, and Cajal bodies
eLife 5:e18221.
https://doi.org/10.7554/eLife.18221
