Structure and folding of the Tetrahymena telomerase RNA pseudoknot

Cash, Darian D.; Feigon, Juli

doi:10.1093/nar/gkw1153

Structure and folding of the Tetrahymena telomerase RNA pseudoknot

Journal Article · Mon Nov 28 00:00:00 EST 2016 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkw1153· OSTI ID:1361669

Cash, Darian D. ^[1]; Feigon, Juli ^[2]

Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry. Molecular Biology Inst.; University of California
Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry. Molecular Biology Inst.

Telomerase maintains telomere length at the ends of linear chromosomes using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT). An essential part of TER is the template/pseudoknot domain (t/PK) which includes the template, for adding telomeric repeats, template boundary element (TBE), and pseudoknot, enclosed in a circle by stem 1. The Tetrahymena telomerase holoenzyme catalytic core (p65-TER-TERT) was recently modeled in our 9 Å resolution cryo-electron microscopy map by fitting protein and TER domains, including a solution NMR structure of the Tetrahymena pseudoknot. Here, we describe in detail the structure and folding of the isolated pseudoknot, which forms a compact structure with major groove U•A-U and novel C•G-A⁺ base triples. Base substitutions that disrupt the base triples reduce telomerase activity in vitro. NMR studies also reveal that the pseudoknot does not form in the context of full-length TER in the absence of TERT, due to formation of a competing structure that sequesters pseudoknot residues. The residues around the TBE remain unpaired, potentially providing access by TERT to this high affinity binding site during an early step in TERT-TER assembly. A model for the assembly pathway of the catalytic core is proposed.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of California, Los Angeles, CA (United States)

Sponsoring Organization:: National Inst. of Health (NIH) (United States); National Science Foundation (NSF) (United States); USDOE

Grant/Contract Number:: FC03-02ER63421

OSTI ID:: 1361669

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 1 Vol. 45; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

References (106)

Single-Molecule FRET Reveals the Folding Dynamics of the Human Telomerase RNA Pseudoknot Domain Hengesbach, Martin; Kim, Nak-Kyoon; Feigon, Juli Angewandte Chemie, Vol. 124, Issue 24 https://doi.org/10.1002/ange.201200526	journal	April 2012
Architecture of telomerase RNA. Bhattacharyya, A.; Blackburn, E. H. The EMBO Journal, Vol. 13, Issue 23 https://doi.org/10.1002/j.1460-2075.1994.tb06910.x	journal	December 1994
31P Chemical Shift as a Probe of Structural Motifs in RNA Legault, P.; Pardi, A. Journal of Magnetic Resonance, Series B, Vol. 103, Issue 1 https://doi.org/10.1006/jmrb.1994.1012	journal	January 1994
A conserved secondary structure for telomerase RNA Romero, Daniel P.; Blackburn, Elizabeth H. Cell, Vol. 67, Issue 2 https://doi.org/10.1016/0092-8674(91)90186-3	journal	October 1991
Solution Structure and Dynamics of the Wild-type Pseudoknot of Human Telomerase RNA Kim, Nak-Kyoon; Zhang, Qi; Zhou, Jing Journal of Molecular Biology, Vol. 384, Issue 5 https://doi.org/10.1016/j.jmb.2008.10.005	journal	December 2008
Structure of the Human Telomerase RNA Pseudoknot Reveals Conserved Tertiary Interactions Essential for Function Theimer, Carla A.; Blois, Craig A.; Feigon, Juli Molecular Cell, Vol. 17, Issue 5 https://doi.org/10.1016/j.molcel.2005.01.017	journal	March 2005
Structural and Functional Characterization of Human Telomerase RNA Processing and Cajal Body Localization Signals Theimer, Carla A.; Jády, Beáta E.; Chim, Nicholas Molecular Cell, Vol. 27, Issue 6 https://doi.org/10.1016/j.molcel.2007.07.017	journal	September 2007
Structural Basis for Telomerase RNA Recognition and RNP Assembly by the Holoenzyme La Family Protein p65 Singh, Mahavir; Wang, Zhonghua; Koo, Bon-Kyung Molecular Cell, Vol. 47, Issue 1 https://doi.org/10.1016/j.molcel.2012.05.018	journal	July 2012
Telomerase structure function Mason, Mark; Schuller, Anthony; Skordalakes, Emmanuel Current Opinion in Structural Biology, Vol. 21, Issue 1 https://doi.org/10.1016/j.sbi.2010.11.005	journal	February 2011
Improving NMR Structures of RNA Bermejo, Guillermo A.; Clore, G. Marius; Schwieters, Charles D. Structure, Vol. 24, Issue 5 https://doi.org/10.1016/j.str.2016.03.007	journal	May 2016
Secondary Structure of Vertebrate Telomerase RNA Chen, Jiunn-Liang; Blasco, Maria A.; Greider, Carol W. Cell, Vol. 100, Issue 5 https://doi.org/10.1016/s0092-8674(00)80687-x	journal	March 2000
Beginning to Understand the End of the Chromosome Cech, Thomas R. Cell, Vol. 116, Issue 2 https://doi.org/10.1016/s0092-8674(04)00038-8	journal	January 2004
The Xplor-NIH NMR molecular structure determination package Schwieters, Charles D.; Kuszewski, John J.; Tjandra, Nico Journal of Magnetic Resonance, Vol. 160, Issue 1 https://doi.org/10.1016/s1090-7807(02)00014-9	journal	January 2003
Distinct Biogenesis Pathways for Human Telomerase RNA and H/ACA Small Nucleolar RNAs Fu, Dragony; Collins, Kathleen Molecular Cell, Vol. 11, Issue 5 https://doi.org/10.1016/s1097-2765(03)00196-5	journal	May 2003
Roles for RNA in Telomerase Nucleotide and Repeat Addition Processivity Lai, Cary K.; Miller, Michael C.; Collins, Kathleen Molecular Cell, Vol. 11, Issue 6 https://doi.org/10.1016/s1097-2765(03)00232-6	journal	June 2003
Identification by modification-interference of purine N-7 and ribose 2′-OH groups critical for catalysis by bacterial ribonuclease P Kazantsev, Alexei V.; Pace, Norman R. RNA, Vol. 4, Issue 8 https://doi.org/10.1017/s1355838298980384	journal	August 1998
A Stem−Loop of Tetrahymena Telomerase RNA Distant from the Template Potentiates RNA Folding and Telomerase Activity ^† Sperger, Jamie M.; Cech, Thomas R. Biochemistry, Vol. 40, Issue 24 https://doi.org/10.1021/bi0103359	journal	June 2001
Crystal Structure of an RNA 16-mer Duplex R(GCAGAGUUAAAUCUGC) ₂ with Nonadjacent G(Syn)·A ⁺ (Anti) Mispairs ^† Pan, Baocheng; Mitra, Shome Nath; Sundaralingam, Muttaiya Biochemistry, Vol. 38, Issue 9 https://doi.org/10.1021/bi982122y	journal	March 1999
New Models of Tetrahymena Telomerase RNA from Experimentally Derived Constraints and Modeling Cole, Daud I.; Legassie, Jason D.; Bonifacio, Laura N. Journal of the American Chemical Society, Vol. 134, Issue 49 https://doi.org/10.1021/ja305636u	journal	December 2012
New applications of 2D filtered/edited NOESY for assignment and structure elucidation of RNA and RNA-protein complexes Peterson, Robert D.; Theimer, Carla A.; Wu, Haihong Journal of Biomolecular NMR, Vol. 28, Issue 1 https://doi.org/10.1023/b:jnmr.0000012861.95939.05	journal	January 2004
Formation of a stable triplex from a single DNA strand Sklenár̆, Vladmír; Felgon, Juli Nature, Vol. 345, Issue 6278 https://doi.org/10.1038/345836a0	journal	June 1990
Tunable alignment of macromolecules by filamentous phage yields dipolar coupling interactions Hansen, Mark R.; Mueller, Luciano; Pardi, Arthur Nature Structural Biology, Vol. 5, Issue 12 https://doi.org/10.1038/4176	journal	December 1998
Stepwise protein-mediated RNA folding directs assembly of telomerase ribonucleoprotein Stone, Michael D.; Mihalusova, Mariana; O’Connor, Catherine M. Nature, Vol. 446, Issue 7134 https://doi.org/10.1038/nature05600	journal	February 2007
Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging Blackburn, Elizabeth H.; Greider, Carol W.; Szostak, Jack W. Nature Medicine, Vol. 12, Issue 10 https://doi.org/10.1038/nm1006-1133	journal	October 2006
Direct detection of N−H⋯N hydrogen bonds in biomolecules by NMR spectroscopy Dingley, Andrew J.; Nisius, Lydia; Cordier, Florence Nature Protocols, Vol. 3, Issue 2 https://doi.org/10.1038/nprot.2007.497	journal	January 2008
The biogenesis and regulation of telomerase holoenzymes Collins, Kathleen Nature Reviews Molecular Cell Biology, Vol. 7, Issue 7 https://doi.org/10.1038/nrm1961	journal	July 2006
Finding the end: recruitment of telomerase to telomeres Nandakumar, Jayakrishnan; Cech, Thomas R. Nature Reviews Molecular Cell Biology, Vol. 14, Issue 2 https://doi.org/10.1038/nrm3505	journal	January 2013
Triple-helix structure in telomerase RNA contributes to catalysis Qiao, Feng; Cech, Thomas R. Nature Structural & Molecular Biology, Vol. 15, Issue 6 https://doi.org/10.1038/nsmb.1420	journal	May 2008
Structural basis for protein-RNA recognition in telomerase Huang, Jing; Brown, Andrew F.; Wu, Jian Nature Structural & Molecular Biology, Vol. 21, Issue 6 https://doi.org/10.1038/nsmb.2819	journal	May 2014
Structural basis of template-boundary definition in Tetrahymena telomerase Jansson, Linnea I.; Akiyama, Ben M.; Ooms, Alexandra Nature Structural & Molecular Biology, Vol. 22, Issue 11 https://doi.org/10.1038/nsmb.3101	journal	October 2015
A telomerase holoenzyme protein enhances telomerase RNA assembly with telomerase reverse transcriptase Prathapam, Ramadevi; Witkin, Keren L.; O'Connor, Catherine M. Nature Structural & Molecular Biology, Vol. 12, Issue 3 https://doi.org/10.1038/nsmb900	journal	February 2005
A mutation in T7 RNA polymerase that facilitates promoter clearance Guillerez, J.; Lopez, P. J.; Proux, F. Proceedings of the National Academy of Sciences, Vol. 102, Issue 17 https://doi.org/10.1073/pnas.0407141102	journal	April 2005
Functional importance of telomerase pseudoknot revealed by single-molecule analysis Mihalusova, M.; Wu, J. Y.; Zhuang, X. Proceedings of the National Academy of Sciences, Vol. 108, Issue 51 https://doi.org/10.1073/pnas.1017686108	journal	May 2011
Telomerase recognizes its template by using an adjacent RNA motif Miller, M. C.; Collins, K. Proceedings of the National Academy of Sciences, Vol. 99, Issue 10 https://doi.org/10.1073/pnas.102024699	journal	May 2002
RNA-protein binding interface in the telomerase ribonucleoprotein Bley, C. J.; Qi, X.; Rand, D. P. Proceedings of the National Academy of Sciences, Vol. 108, Issue 51 https://doi.org/10.1073/pnas.1100270108	journal	November 2011
The telomerase RNA pseudoknot is critical for the stable assembly of a catalytically active ribonucleoprotein Gilley, D.; Blackburn, E. H. Proceedings of the National Academy of Sciences, Vol. 96, Issue 12 https://doi.org/10.1073/pnas.96.12.6621	journal	June 1999
A Mutant of Tetrahymena Telomerase Reverse Transcriptase with Increased Processivity Bryan, Tracy M.; Goodrich, Karen J.; Cech, Thomas R. Journal of Biological Chemistry, Vol. 275, Issue 31 https://doi.org/10.1074/jbc.m003246200	journal	May 2000
A novel family of RNA tetraloop structure forms the recognition site for Saccharomyces cerevisiae RNase III Wu, H. The EMBO Journal, Vol. 20, Issue 24 https://doi.org/10.1093/emboj/20.24.7240	journal	December 2001
A conserved pseudoknot in telomerase RNA Dam, Edwin ten; Belkum, Alex van; Pleij, Kees Nucleic Acids Research, Vol. 19, Issue 24 https://doi.org/10.1093/nar/19.24.6951	journal	January 1991
Mutational analysis of the Tetrahymena telomerase RNA: identification of residues affecting telomerase activity in vitro Autexier, C. Nucleic Acids Research, Vol. 26, Issue 3 https://doi.org/10.1093/nar/26.3.787	journal	February 1998
The solution structure of an essential stem-loop of human telomerase RNA Leeper, T. Nucleic Acids Research, Vol. 31, Issue 10 https://doi.org/10.1093/nar/gkg351	journal	May 2003
Structure of the Tetrahymena thermophila telomerase RNA helix II template boundary element Richards, R. J. Nucleic Acids Research, Vol. 34, Issue 3 https://doi.org/10.1093/nar/gkj481	journal	February 2006
Inventory of telomerase components in human cells reveals multiple subpopulations of hTR and hTERT Xi, Linghe; Cech, Thomas R. Nucleic Acids Research, Vol. 42, Issue 13 https://doi.org/10.1093/nar/gku560	journal	July 2014
Phylogenetic relationships amongst tetrahymenine ciliates inferred by a comparison of telomerase RNAs. Ye, Amanda J.; Romero, Daniel P. International Journal of Systematic and Evolutionary Microbiology, Vol. 52, Issue 6 https://doi.org/10.1099/00207713-52-6-2297	journal	November 2002
Telomerase: An RNP Enzyme Synthesizes DNA Blackburn, E. H.; Collins, K. Cold Spring Harbor Perspectives in Biology, Vol. 3, Issue 5 https://doi.org/10.1101/cshperspect.a003558	journal	July 2010
A novel pseudoknot element is essential for the action of a yeast telomerase Tzfati, Y. Genes & Development, Vol. 17, Issue 14 https://doi.org/10.1101/gad.1099403	journal	July 2003
Telomerase RNA function in recombinant Tetrahymena telomerase Licht, J. D.; Collins, K. Genes & Development, Vol. 13, Issue 9 https://doi.org/10.1101/gad.13.9.1116	journal	May 1999
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/s0907444904019158	journal	November 2004
Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions Jiang, J.; Chan, H.; Cash, D. D. Science, Vol. 350, Issue 6260 https://doi.org/10.1126/science.aab4070	journal	October 2015
Tetrahymena Telomerase Protein p65 Induces Conformational Changes throughout Telomerase RNA (TER) and Rescues Telomerase Reverse Transcriptase and TER Assembly Mutants Berman, A. J.; Gooding, A. R.; Cech, T. R. Molecular and Cellular Biology, Vol. 30, Issue 20 https://doi.org/10.1128/mcb.00827-10	journal	August 2010
Comprehensive Structure-Function Analysis of the Core Domain of Human Telomerase RNA Ly, H.; Blackburn, E. H.; Parslow, T. G. Molecular and Cellular Biology, Vol. 23, Issue 19 https://doi.org/10.1128/mcb.23.19.6849-6856.2003	journal	September 2003
Biological and Biochemical Functions of RNA in the Tetrahymena Telomerase Holoenzyme Cunningham, Doreen D.; Collins, Kathleen Molecular and Cellular Biology, Vol. 25, Issue 11 https://doi.org/10.1128/mcb.25.11.4442-4454.2005	journal	June 2005
Thermodynamic characterization of the Saccharomyces cerevisiae telomerase RNA pseudoknot domain in vitro Liu, F.; Kim, Y.; Cruickshank, C. RNA, Vol. 18, Issue 5 https://doi.org/10.1261/rna.030924.111	journal	March 2012
Biogenesis of telomerase ribonucleoproteins Egan, E. D.; Collins, K. RNA, Vol. 18, Issue 10 https://doi.org/10.1261/rna.034629.112	journal	August 2012
The structure of an enzyme-activating fragment of human telomerase RNA Leeper, T. C. RNA, Vol. 11, Issue 4 https://doi.org/10.1261/rna.7222505	journal	April 2005
Structure of stem-loop IV of Tetrahymena telomerase RNA D., Legassie, Jason; B., Jarstfer, Michael; Yu, Chen, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/5gxd-tx15	text	January 2006
Structure and sequence elements of the CR4/5 domain of medaka telomerase RNA important for telomerase function Kyoon, Kim, Nak; Qi, Zhang,; Juli, Feigon, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/k7gr-f763	text	January 2014
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids B., Chen, Vincent; C., Richardson, David; S., Richardson, Jane The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/m2an-p252	text	January 2007
Single-Molecule FRET Reveals the Folding Dynamics of the Human Telomerase RNA Pseudoknot Domain Hengesbach, Martin; Kim, Nak-Kyoon; Feigon, Juli Angewandte Chemie International Edition, Vol. 51, Issue 24 https://doi.org/10.1002/anie.201200526	journal	April 2012
Reconstitution of human telomerase activity and identification of a minimal functional region of the human telomerase RNA. Autexier, C.; Pruzan, R.; Funk, W. D. The EMBO Journal, Vol. 15, Issue 21 https://doi.org/10.1002/j.1460-2075.1996.tb00979.x	journal	November 1996
Identification of a specific telomere terminal transferase activity in tetrahymena extracts Greider, Carol W.; Blackburn, Elizabeth H. Cell, Vol. 43, Issue 2 https://doi.org/10.1016/0092-8674(85)90170-9	journal	December 1985
RNA Purification by Preparative Polyacrylamide Gel Electrophoresis Petrov, Alexey; Wu, Tinghe; Puglisi, Elisabetta Viani Laboratory Methods in Enzymology: RNA https://doi.org/10.1016/B978-0-12-420037-1.00017-8	book	January 2013
NMR dipolar couplings for the structure determination of biopolymers in solution de Alba, Eva; Tjandra, Nico Progress in Nuclear Magnetic Resonance Spectroscopy, Vol. 40, Issue 2 https://doi.org/10.1016/S0079-6565(01)00042-5	journal	February 2002
Secondary Structure of Vertebrate Telomerase RNA Chen, Jiunn-Liang; Blasco, Maria A.; Greider, Carol W. Cell, Vol. 100, Issue 5 https://doi.org/10.1016/S0092-8674(00)80687-X	journal	March 2000
Switching and Signaling at the Telomere Blackburn, Elizabeth H. Cell, Vol. 106, Issue 6 https://doi.org/10.1016/S0092-8674(01)00492-5	journal	September 2001
Biochemical aspects of telomerase function Harrington, Lea Cancer Letters, Vol. 194, Issue 2 https://doi.org/10.1016/S0304-3835(02)00701-2	journal	May 2003
The Xplor-NIH NMR molecular structure determination package Schwieters, Charles D.; Kuszewski, John J.; Tjandra, Nico Journal of Magnetic Resonance, Vol. 160, Issue 1 https://doi.org/10.1016/S1090-7807(02)00014-9	journal	January 2003
Distinct Biogenesis Pathways for Human Telomerase RNA and H/ACA Small Nucleolar RNAs Fu, Dragony; Collins, Kathleen Molecular Cell, Vol. 11, Issue 5 https://doi.org/10.1016/S1097-2765(03)00196-5	journal	May 2003
Roles for RNA in Telomerase Nucleotide and Repeat Addition Processivity Lai, Cary K.; Miller, Michael C.; Collins, Kathleen Molecular Cell, Vol. 11, Issue 6 https://doi.org/10.1016/S1097-2765(03)00232-6	journal	June 2003
Large telomerase RNA, telomere length heterogeneity and escape from senescence in Candida glabrata Kachouri-Lafond, R.; Dujon, B.; Gilson, E. FEBS Letters, Vol. 583, Issue 22 https://doi.org/10.1016/j.febslet.2009.10.034	journal	October 2009
Identification by modification-interference of purine N-7 and ribose 2′-OH groups critical for catalysis by bacterial ribonuclease P Kazantsev, Alexei V.; Pace, Norman R. RNA, Vol. 4, Issue 8 https://doi.org/10.1017/S1355838298980384	journal	August 1998
A sensitive genetic assay for the detection of cytosine deamination: determination of rate constants and the activation energy Frederico, Lisa A.; Kunkel, Thomas A.; Shaw, Barbara Ramsay Biochemistry, Vol. 29, Issue 10 https://doi.org/10.1021/bi00462a015	journal	March 1990
Direct Observation of Hydrogen Bonds in Nucleic Acid Base Pairs by Internucleotide ² J _NN Couplings Dingley, Andrew J.; Grzesiek, Stephan Journal of the American Chemical Society, Vol. 120, Issue 33 https://doi.org/10.1021/ja981513x	journal	August 1998
Prediction of proton chemical shifts in RNA – Their use in structure refinement and validation Cromsigt, Jenny A. M. T. C.; Hilbers, Cees W.; Wijmenga, Sybren S. Journal of Biomolecular NMR, Vol. 21, Issue 1, p. 11-29 https://doi.org/10.1023/A:1011914132531	journal	January 2001
Assignment methodology for larger RNA oligonucleotides: Application to an ATP-binding RNA aptamer Dieckmann, Thorsten; Feigon, Juli Journal of Biomolecular NMR, Vol. 9, Issue 3, p. 259-272 https://doi.org/10.1023/A:1018622708674	journal	April 1997
New applications of 2D filtered/edited NOESY for assignment and structure elucidation of RNA and RNA-protein complexes Peterson, Robert D.; Theimer, Carla A.; Wu, Haihong Journal of Biomolecular NMR, Vol. 28, Issue 1 https://doi.org/10.1023/B:JNMR.0000012861.95939.05	journal	January 2004
Three-dimensional structure of a hammerhead ribozyme Pley, Heinz W.; Flaherty, Kevin M.; McKay, David B. Nature, Vol. 372, Issue 6501 https://doi.org/10.1038/372068a0	journal	November 1994
Minor groove RNA triplex in the crystal structure of a ribosomal frameshifting viral pseudoknot Rich, Alexander; Su, Li; Chen, Liqing Nature Structural Biology, Vol. 6, Issue 3, p. 285-292 https://doi.org/10.1038/6722	journal	March 1999
The end of the (DNA) line Blackburn, Elizabeth H. Nature Structural Biology, Vol. 7, Issue 10, p. 847-850 https://doi.org/10.1038/79594	journal	October 2000
The architecture of Tetrahymena telomerase holoenzyme Jiang, Jiansen; Miracco, Edward J.; Hong, Kyungah Nature, Vol. 496, Issue 7444 https://doi.org/10.1038/nature12062	journal	April 2013
Telomeres: protecting chromosomes against genome instability O'Sullivan, Roderick J.; Karlseder, Jan Nature Reviews Molecular Cell Biology, Vol. 11, Issue 3 https://doi.org/10.1038/nrm2848	journal	February 2010
Structure of stem-loop IV of Tetrahymena telomerase RNA Chen, Yu; Fender, Jessica; Legassie, Jason D. The EMBO Journal, Vol. 25, Issue 13 https://doi.org/10.1038/sj.emboj.7601195	journal	June 2006
A universal telomerase RNA core structure includes structured motifs required for binding the telomerase reverse transcriptase protein Lin, J.; Ly, H.; Hussain, A. Proceedings of the National Academy of Sciences, Vol. 101, Issue 41 https://doi.org/10.1073/pnas.0405879101	journal	September 2004
Functional analysis of the pseudoknot structure in human telomerase RNA Chen, J. -L.; Greider, C. W. Proceedings of the National Academy of Sciences, Vol. 102, Issue 23 https://doi.org/10.1073/pnas.0502259102	journal	April 2005
Pyrimidine motif triple helix in the Kluyveromyces lactis telomerase RNA pseudoknot is essential for function in vivo Cash, D. D.; Cohen-Zontag, O.; Kim, N. -K. Proceedings of the National Academy of Sciences, Vol. 110, Issue 27 https://doi.org/10.1073/pnas.1309590110	journal	June 2013
Mutations linked to dyskeratosis congenita cause changes in the structural equilibrium in telomerase RNA Theimer, C. A.; Finger, L. D.; Trantirek, L. Proceedings of the National Academy of Sciences, Vol. 100, Issue 2 https://doi.org/10.1073/pnas.242720799	journal	January 2003
A Mutant of Tetrahymena Telomerase Reverse Transcriptase with Increased Processivity Bryan, Tracy M.; Goodrich, Karen J.; Cech, Thomas R. Journal of Biological Chemistry, Vol. 275, Issue 31 https://doi.org/10.1074/jbc.M003246200	journal	May 2000
Roles of Telomerase Reverse Transcriptase N-terminal Domain in Assembly and Activity of Tetrahymena Telomerase Holoenzyme Eckert, Barbara; Collins, Kathleen Journal of Biological Chemistry, Vol. 287, Issue 16 https://doi.org/10.1074/jbc.M112.339853	journal	February 2012
Preparation of isotopically labeled ribonucleotides for multidimensional NMR spectroscopy of RNA Batey, Robert T.; Inada, Maki; Kujawinski, Elizabeth Nucleic Acids Research, Vol. 20, Issue 17 https://doi.org/10.1093/nar/20.17.4515	journal	January 1992
A human-Tetrahymena pseudoknot chimeric telomerase RNA reconstitutes a nonprocessive enzyme in vitro that is defective in telomere elongation Marie-Egyptienne, D. T. Nucleic Acids Research, Vol. 33, Issue 17 https://doi.org/10.1093/nar/gki848	journal	September 2005
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids Davis, I. W.; Leaver-Fay, A.; Chen, V. B. Nucleic Acids Research, Vol. 35, Issue Web Server https://doi.org/10.1093/nar/gkm216	journal	May 2007
Pseudoknot structures with conserved base triples in telomerase RNAs of ciliates Ulyanov, Nikolai B.; Shefer, Kinneret; James, Thomas L. Nucleic Acids Research, Vol. 35, Issue 18 https://doi.org/10.1093/nar/gkm660	journal	September 2007
Comprehensive survey and geometric classification of base triples in RNA structures Abu Almakarem, Amal S.; Petrov, Anton I.; Stombaugh, Jesse Nucleic Acids Research, Vol. 40, Issue 4 https://doi.org/10.1093/nar/gkr810	journal	November 2011
Automated 3D structure composition for large RNAs Popenda, Mariusz; Szachniuk, Marta; Antczak, Maciej Nucleic Acids Research, Vol. 40, Issue 14 https://doi.org/10.1093/nar/gks339	journal	April 2012
Structure and sequence elements of the CR4/5 domain of medaka telomerase RNA important for telomerase function Kim, Nak-Kyoon; Zhang, Qi; Feigon, Juli Nucleic Acids Research, Vol. 42, Issue 5 https://doi.org/10.1093/nar/gkt1276	journal	December 2013
Phylogenetic relationships amongst tetrahymenine ciliates inferred by a comparison of telomerase RNAs Ye, A. J. INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, Vol. 52, Issue 6 https://doi.org/10.1099/ijs.0.02183-0	journal	November 2002
Template boundary definition in Tetrahymena telomerase Lai, C. K. Genes & Development, Vol. 16, Issue 4 https://doi.org/10.1101/gad.962602	journal	February 2002
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Tetrahymena Telomerase Holoenzyme Assembly, Activation, and Inhibition by Domains of the p50 Central Hub Hong, K.; Upton, H.; Miracco, E. J. Molecular and Cellular Biology, Vol. 33, Issue 19 https://doi.org/10.1128/MCB.00792-13	journal	August 2013
Tetrahymena Telomerase Protein p65 Induces Conformational Changes throughout Telomerase RNA (TER) and Rescues Telomerase Reverse Transcriptase and TER Assembly Mutants Berman, A. J.; Gooding, A. R.; Cech, T. R. Molecular and Cellular Biology, Vol. 30, Issue 20 https://doi.org/10.1128/MCB.00827-10	journal	August 2010
A Triple Helix within a Pseudoknot Is a Conserved and Essential Element of Telomerase RNA Shefer, Kinneret; Brown, Yogev; Gorkovoy, Valentin Molecular and Cellular Biology, Vol. 27, Issue 6 https://doi.org/10.1128/MCB.01826-06	journal	January 2007
Comprehensive Structure-Function Analysis of the Core Domain of Human Telomerase RNA Ly, H.; Blackburn, E. H.; Parslow, T. G. Molecular and Cellular Biology, Vol. 23, Issue 19 https://doi.org/10.1128/MCB.23.19.6849-6856.2003	journal	September 2003
Biological and Biochemical Functions of RNA in the Tetrahymena Telomerase Holoenzyme Cunningham, Doreen D.; Collins, Kathleen Molecular and Cellular Biology, Vol. 25, Issue 11 https://doi.org/10.1128/MCB.25.11.4442-4454.2005	journal	June 2005
A Novel RNA Binding Domain in Tetrahymena Telomerase p65 Initiates Hierarchical Assembly of Telomerase Holoenzyme O'Connor, C. M.; Collins, K. Molecular and Cellular Biology, Vol. 26, Issue 6 https://doi.org/10.1128/MCB.26.6.2029-2036.2006	journal	February 2006
The C-terminal domain of Tetrahymena thermophila telomerase holoenzyme protein p65 induces multiple structural changes in telomerase RNA Akiyama, B. M.; Loper, J.; Najarro, K. RNA, Vol. 18, Issue 4 https://doi.org/10.1261/rna.031377.111	journal	February 2012
Structural study of elements of Tetrahymena telomerase RNA stem-loop IV domain important for function Richards, R. J. RNA, Vol. 12, Issue 8 https://doi.org/10.1261/rna.112306	journal	June 2006

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Detailed view of human telomerase enzyme invites rethink of its structure Stone, Michael D. Nature, Vol. 557, Issue 7704 https://doi.org/10.1038/d41586-018-04756-3	journal	April 2018
Mechanisms of template handling and pseudoknot folding in human telomerase and their manipulation to expand the sequence repertoire of processive repeat synthesis Deshpande, Aishwarya P.; Collins, Kathleen Nucleic Acids Research, Vol. 46, Issue 15 https://doi.org/10.1093/nar/gky601	journal	July 2018
Zika genomics urgently need standardized and curated reference sequences Theys, Kristof; Libin, Pieter; Dallmeier, Kai PLOS Pathogens, Vol. 13, Issue 9 https://doi.org/10.1371/journal.ppat.1006528	journal	September 2017
Current Perspectives of Telomerase Structure and Function in Eukaryotes with Emerging Views on Telomerase in Human Parasites Dey, Abhishek; Chakrabarti, Kausik International Journal of Molecular Sciences, Vol. 19, Issue 2 https://doi.org/10.3390/ijms19020333	journal	January 2018
New perspectives on telomerase RNA structure and function: Telomerase RNA structure and function Musgrove, Cherie; Jansson, Linnea I.; Stone, Michael D. Wiley Interdisciplinary Reviews: RNA, Vol. 9, Issue 2 https://doi.org/10.1002/wrna.1456	journal	November 2017
Cryo-EM structure of substrate-bound human telomerase holoenzyme Nguyen, Thi Hoang Duong; Tam, Jane; Wu, Robert A. Nature, Vol. 557, Issue 7704 https://doi.org/10.1038/s41586-018-0062-x	journal	April 2018
Structural Biology of Telomerase Wang, Yaqiang; Sušac, Lukas; Feigon, Juli Cold Spring Harbor Perspectives in Biology, Vol. 11, Issue 12 https://doi.org/10.1101/cshperspect.a032383	journal	August 2019

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Structure and folding of the Tetrahymena telomerase RNA pseudoknot

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