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Science 5 May 2000:
Vol. 288. no. 5467, pp. 863 - 867
DOI: 10.1126/science.288.5467.863
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Reports

Template Boundary in a Yeast Telomerase Specified by RNA Structure

Yehuda Tzfati, Tracy B. Fulton, Jagoree Roy, Elizabeth H. Blackburn *

The telomerase ribonucleoprotein has a phylogenetically divergent RNA subunit, which contains a short template for telomeric DNA synthesis. To understand how telomerase RNA participates in mechanistic aspects of telomere synthesis, we studied a conserved secondary structure adjacent to the template. Disruption of this structure caused DNA synthesis to proceed beyond the normal template boundary, resulting in altered telomere sequences, telomere shortening, and cellular growth defects. Compensatory mutations restored normal telomerase function. Thus, the RNA structure, rather than its sequence, specifies the template boundary. This study reveals a specific function for an RNA structure in the enzymatic action of telomerase.

Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143-0414, USA.
*   To whom correspondence should be addressed. E-mail: telomer{at}itsa.ucsf.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Y. Brown, M. Abraham, S. Pearl, M. M. Kabaha, E. Elboher, and Y. Tzfati (2007)
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Structure of the Tetrahymena thermophila telomerase RNA helix II template boundary element.
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Human Telomerase RNA Template Sequence Is a Determinant of Telomere Repeat Extension Rate.
W. C. Drosopoulos, R. DiRenzo, and V. R. Prasad (2005)
J. Biol. Chem. 280, 32801-32810
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Regulation of 5' template usage and incorporation of noncognate nucleotides by human telomerase.
T. J. MORIARTY, D. T. MARIE-EGYPTIENNE, and C. AUTEXIER (2005)
RNA 11, 1448-1460
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Processive Utilization of the Human Telomerase Template: LACK OF A REQUIREMENT FOR TEMPLATE SWITCHING.
M. A. Rivera and E. H. Blackburn (2004)
J. Biol. Chem. 279, 53770-53781
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From the Cover: A universal telomerase RNA core structure includes structured motifs required for binding the telomerase reverse transcriptase protein.
J. Lin, H. Ly, A. Hussain, M. Abraham, S. Pearl, Y. Tzfati, T. G. Parslow, and E. H. Blackburn (2004)
PNAS 101, 14713-14718
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Structural Elements Required for Association of the Saccharomyces cerevisiae Telomerase RNA with the Est2 Reverse Transcriptase.
A. S. Chappell and V. Lundblad (2004)
Mol. Cell. Biol. 24, 7720-7736
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Genetic Dissection of the Kluyveromyces lactis Telomere and Evidence for Telomere Capping Defects in TER1 Mutants with Long Telomeres.
D. H. Underwood, C. Carroll, and M. J. McEachern (2004)
Eukaryot. Cell 3, 369-384
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Mutant Telomere Sequences Lead to Impaired Chromosome Separation and a Unique Checkpoint Response.
J. Lin, D. L. Smith, and E. H. Blackburn (2004)
Mol. Biol. Cell 15, 1623-1634
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Template Requirements for Telomerase Translocation in Kluyveromyces lactis.
D. H. Underwood, R. P. Zinzen, and M. J. McEachern (2004)
Mol. Cell. Biol. 24, 912-923
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Yeast telomerase is capable of limited repeat addition processivity.
D. Bosoy and N. F. Lue (2004)
Nucleic Acids Res. 32, 93-101
   Abstract »    Full Text »    PDF »
A Conserved Telomerase Motif within the Catalytic Domain of Telomerase Reverse Transcriptase Is Specifically Required for Repeat Addition Processivity.
N. F. Lue, Y.-C. Lin, and I. S. Mian (2003)
Mol. Cell. Biol. 23, 8440-8449
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Template boundary definition in mammalian telomerase.
J.-L. Chen and C. W. Greider (2003)
Genes & Dev. 17, 2747-2752
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A template-proximal RNA paired element contributes to Saccharomyces cerevisiae telomerase activity.
A. G. SETO, K. UMANSKY, Y. TZFATI, A. J. ZAUG, E. H. BLACKBURN, and T. R. CECH (2003)
RNA 9, 1323-1332
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A novel pseudoknot element is essential for the action of a yeast telomerase.
Y. Tzfati, Z. Knight, J. Roy, and E. H. Blackburn (2003)
Genes & Dev. 17, 1779-1788
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Conserved N-terminal Motifs of Telomerase Reverse Transcriptase Required for Ribonucleoprotein Assembly in Vivo.
D. Bosoy, Y. Peng, I. S. Mian, and N. F. Lue (2003)
J. Biol. Chem. 278, 3882-3890
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Analysis of Telomerase in Candida albicans: Potential Role in Telomere End Protection.
S. M. Singh, O. Steinberg-Neifach, I. S. Mian, and N. F. Lue (2002)
Eukaryot. Cell 1, 967-977
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A bulged stem tethers Est1p to telomerase RNA in budding yeast.
A. G. Seto, A. J. Livengood, Y. Tzfati, E. H. Blackburn, and T. R. Cech (2002)
Genes & Dev. 16, 2800-2812
   Abstract »    Full Text »    PDF »
Functional Analysis of the C-terminal Extension of Telomerase Reverse Transcriptase. A PUTATIVE "THUMB" DOMAIN.
S. Hossain, S. Singh, and N. F. Lue (2002)
J. Biol. Chem. 277, 36174-36180
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Recombinational Telomere Elongation Promoted by DNA Circles.
S. Natarajan and M. J. McEachern (2002)
Mol. Cell. Biol. 22, 4512-4521
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Telomerase recognizes its template by using an adjacent RNA motif.
M. C. Miller and K. Collins (2002)
PNAS 99, 6585-6590
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Template boundary definition in Tetrahymena telomerase.
C. K. Lai, M. C. Miller, and K. Collins (2002)
Genes & Dev. 16, 415-420
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Dynamics of Telomeric DNA Turnover in Yeast.
M. J. McEachern, D. H. Underwood, and E. H. Blackburn (2002)
Genetics 160, 63-73
   Abstract »    Full Text »    PDF »
Functional Analysis of Conserved Residues in the Putative "Finger" Domain of Telomerase Reverse Transcriptase.
D. Bosoy and N. F. Lue (2001)
J. Biol. Chem. 276, 46305-46312
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Functional Regions of Human Telomerase Reverse Transcriptase and Human Telomerase RNA Required for Telomerase Activity and RNA-Protein Interactions.
F. Bachand and C. Autexier (2001)
Mol. Cell. Biol. 21, 1888-1897
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Stabilization of the U5-leader stem in the HIV-1 RNA genome affects initiation and elongation of reverse transcription.
N. Beerens, F. Groot, and B. Berkhout (2000)
Nucleic Acids Res. 28, 4130-4137
   Abstract »    Full Text »    PDF »
Positive and negative regulation of telomerase access to the telomere.
S. Evans and V Lundblad (2000)
J. Cell Sci. 113, 3357-3364
   Abstract »    PDF »


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