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Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle

Abstract

Activation of the chromosome end-replicating enzyme telomerase can greatly extend the lifespan of normal human cells1 and is associated with most human cancers2. In all eukaryotes examined, telomerase has an RNA subunit3, a conserved reverse transcriptase subunit4 and additional proteins5,6, but little is known about the assembly of these components. Here we show that the Saccharomyces cerevisiae telomerase RNA7 has a 5′-2,2,7-trimethylguanosine (TMG) cap and a binding site for the Sm proteins, both hallmarks of small nuclear ribonucleoprotein particles (snRNPs) that are involved in nuclear messenger RNA splicing8,9. Immunoprecipitation of telomerase from yeast extracts shows that Sm proteins are assembled on the RNA and that most or all of the telomerase activity is associated with the Sm-containing complex. These data support a model in which telomerase RNA is transcribed by RNA polymerase II (ref. 10) and 7-methylguanosine-capped, binds the seven Sm proteins, becomes TMG-capped and picks up the other protein subunits. We conclude that the functions of snRNPs assembled by this pathway are not restricted to RNA processing, but also include chromosome telomere replication.

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Figure 1: Identification of 5′-TMG cap on telomerase RNA.
Figure 2: Characterization of mutants in the putative Sm protein binding site.
Figure 3: HA-tagged Smd1 protein co-immunoprecipitates TLC1 RNA and in vitro telomerase activity.

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Acknowledgements

We thank K. Friedman, D. Gottschling, and B. Rymond for yeast plasmids and strains; R. Weilbaecher and V. Lundblad for their telomerase activity assay protocol; and the Cech lab and J. Goodrich for discussions. This work was supported by grants from the NIH to T.R.C. and S.L.W. T.R.C. and S.L.W. are investigators of the Howard Hughes Medical Institute.

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Correspondence to Thomas R. Cech.

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Seto, A., Zaug, A., Sobel, S. et al. Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature 401, 177–180 (1999). https://doi.org/10.1038/43694

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