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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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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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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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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DOI: https://doi.org/10.1038/nsmb.1420
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