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Triple-helix structure in telomerase RNA contributes to catalysis

Nature Structural & Molecular Biology volume 15, pages 634–640 (2008)Cite this article

Abstract

Telomerase is responsible for replication of the ends of linear chromosomes in most eukaryotes. Its intrinsic RNA subunit provides the template for synthesis of telomeric DNA by the reverse-transcriptase (TERT) subunit and tethers other proteins into the ribonucleoprotein (RNP) complex. We report that a phylogenetically conserved triple helix within a pseudoknot structure of this RNA contributes to telomerase activity but not by binding the TERT protein. Instead, 2′-OH groups protruding from the triple helix participate in both yeast and human telomerase catalysis; they may orient the primer-template relative to the active site in a manner analogous to group I ribozymes. The role of RNA in telomerase catalysis may have been acquired relatively recently or, alternatively, telomerase may be a molecular fossil representing an evolutionary link between RNA enzymes and RNP enzymes.

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Figure 1: The core region of the S. cerevisiae telomerase RNA has a conserved pseudoknot RNA structure.
Figure 2: The pseudoknot region of the S. cerevisiae telomerase RNA contains a triple-helix structure.
Figure 3: The triple-helix structure in TLC1 is not responsible for the binding affinity of the reverse-transcriptase subunit, Est2.
Figure 4: The triple-helix region is in close proximity to the 3′ end of the DNA substrate.
Figure 5: The 2′-OH groups in the triple-helix regions of both yeast and human telomerase RNAs are important for catalysis.
Figure 6: The 2′-OH group of A176 in the triple-helix structure of human telomerase RNA is important for catalysis.

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Acknowledgements

We thank V. Lundblad (The Salk Institute for Biological Studies) for providing yeast strains, D. Zappulla for help with yeast telomerase assays and in vivo analysis, A. Zaug and A. Mozdy (University of Colorado, Boulder) for plasmids, Y. Tzfati for sharing results before publication and A. Berman for helpful comments on the manuscript. F.Q. is a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation. This work was supported in part by the US National Institutes of Health grant R01 GM28039.

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  1. Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, Campus Box 215, University of Colorado, Boulder, 80309-0215, Colorado, USA

    Feng Qiao & Thomas R Cech

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  1. Feng Qiao
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  2. Thomas R Cech
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Contributions

F.Q. and T.R.C. conceived and designed the study; F.Q. performed the experiments; and F.Q. and T.R.C. analyzed the results and wrote the paper.

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Correspondence to Thomas R Cech.

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Qiao, F., Cech, T. Triple-helix structure in telomerase RNA contributes to catalysis. Nat Struct Mol Biol 15, 634–640 (2008). https://doi.org/10.1038/nsmb.1420

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