scholarly journals Elucidation of the mode of interaction in the UP1-telomerase RNA-telomeric DNA ternary complex which serves to recruit telomerase to telomeric DNA and to enhance the telomerase activity

2008 ◽  
Vol 36 (21) ◽  
pp. 6816-6824 ◽  
Author(s):  
T. Nagata ◽  
Y. Takada ◽  
A. Ono ◽  
K. Nagata ◽  
Y. Konishi ◽  
...  
Keyword(s):  
Ternary Complex ◽  
Telomerase Activity ◽  
Telomerase Rna ◽  
Telomeric Dna

scholarly journals The conserved structure of plant telomerase RNA provides the missing link for an evolutionary pathway from ciliates to humans

2019 ◽  
Vol 116 (49) ◽  
pp. 24542-24550 ◽  
Author(s):  
Jiarui Song ◽  
Dhenugen Logeswaran ◽  
Claudia Castillo-González ◽  
Yang Li ◽  
Sreyashree Bose ◽  
...  
Keyword(s):  
Telomerase Activity ◽  
Telomere Maintenance ◽  
Telomerase Rna ◽  
Telomeric Dna ◽  
Structural Element ◽  
Stem Loop ◽  
Evolutionary Pathway ◽  
Pol Iii

Telomerase is essential for maintaining telomere integrity. Although telomerase function is widely conserved, the integral telomerase RNA (TR) that provides a template for telomeric DNA synthesis has diverged dramatically. Nevertheless, TR molecules retain 2 highly conserved structural domains critical for catalysis: a template-proximal pseudoknot (PK) structure and a downstream stem-loop structure. Here we introduce the authentic TR from the plant Arabidopsis thaliana, called AtTR, identified through next-generation sequencing of RNAs copurifying with Arabidopsis TERT. This RNA is distinct from the RNA previously described as the templating telomerase RNA, AtTER1. AtTR is a 268-nt Pol III transcript necessary for telomere maintenance in vivo and sufficient with TERT to reconstitute telomerase activity in vitro. Bioinformatics analysis identified 85 AtTR orthologs from 3 major clades of plants: angiosperms, gymnosperms, and lycophytes. Through phylogenetic comparisons, a secondary structure model conserved among plant TRs was inferred and verified using in vitro and in vivo chemical probing. The conserved plant TR structure contains a template-PK core domain enclosed by a P1 stem and a 3′ long-stem P4/5/6, both of which resemble a corresponding structural element in ciliate and vertebrate TRs. However, the plant TR contains additional stems and linkers within the template-PK core, allowing for expansion of PK structure from the simple PK in the smaller ciliate TR during evolution. Thus, the plant TR provides an evolutionary bridge that unites the disparate structures of previously characterized TRs from ciliates and vertebrates.

scholarly journals Comprehensive Structure-Function Analysis of the Core Domain of Human Telomerase RNA

2003 ◽  
Vol 23 (19) ◽  
pp. 6849-6856 ◽  
Author(s):  
Hinh Ly ◽  
Elizabeth H. Blackburn ◽  
Tristram G. Parslow
Keyword(s):  
Mutational Analysis ◽  
Function Analysis ◽  
Telomerase Activity ◽  
Telomerase Rna ◽  
Dna Repeats ◽  
Telomeric Dna ◽  
Core Domain ◽  
The Core ◽  
Optimal Function ◽  
Human Telomerase

ABSTRACT Telomerase is a cellular reverse transcriptase that uses part of its integral RNA (called TER) as the template to synthesize telomeric DNA repeats. Vertebrate TERs are thought to share a conserved, highly structured core domain that includes the templating sequence and a pseudoknot, but not all features of the predicted core structure have been verified directly or shown to affect telomerase enzymatic activity. Here, we report a systematic mutational analysis of the core domain (residues 1 to 210) of human telomerase RNA (hTER). Our data confirm that optimal hTER activity requires the integrity of four short helices (P2a.1, P2a, P2b, and P3) which create the proposed pseudoknot and that features of both the primary sequence and secondary structure in P2b and P3 contribute to optimal function. At least part of the long-range P1 pairing is also required, despite the lack of a known P1 counterpart in rodent TERs. Among the predicted single-stranded regions, we found that J2b/3, portions of J2a/3, and residues in and around the template make sequence-specific contributions to telomerase function. Additionally, we provide evidence that naturally occurring hTER sequence polymorphisms found in some patients with aplastic anemia can inhibit telomerase activity by disrupting critical structures within the hTER core domain.

scholarly journals The Est1 Subunit of Yeast Telomerase Binds the Tlc1 Telomerase RNA

2000 ◽  
Vol 20 (6) ◽  
pp. 1947-1955 ◽  
Author(s):  
Jianlong Zhou ◽  
Kyoko Hidaka ◽  
Bruce Futcher
Keyword(s):  
Point Mutations ◽  
Telomerase Activity ◽  
Rna Recognition Motif ◽  
Telomerase Rna ◽  
Telomeric Dna ◽  
Reading Frame ◽  
Yeast Telomerase ◽  
Exact Function ◽  
Telomere Loss

ABSTRACT Est1 is a component of yeast telomerase, and est1mutants have senescence and telomere loss phenotypes. The exact function of Est1 is not known, and it is not homologous to components of other telomerases. We previously showed that Est1 protein coimmunoprecipitates with Tlc1 (the telomerase RNA) as well as with telomerase activity. Est1 has homology to Ebs1, an uncharacterized yeast open reading frame product, including homology to a putative RNA recognition motif (RRM) of Ebs1. Deletion of EBS1 results in short telomeres. We created point mutations in a putative RRM of Est1. One mutant was unable to complement either the senescence or the telomere loss phenotype of est1 mutants. Furthermore, the mutant protein no longer coprecipitated with the Tlc1 telomerase RNA. Mutants defective in the binding of Tlc1 RNA were nevertheless capable of binding single-stranded TG-rich DNA. Our data suggest that an important role of Est1 in the telomerase complex is to bind to the Tlc1 telomerase RNA via an RRM. Since Est1 can also bind telomeric DNA, Est1 may tether telomerase to the telomere.

scholarly journals Telomerase activation in mouse mammary tumors: lack of detectable telomere shortening and evidence for regulation of telomerase RNA with cell proliferation.

1996 ◽  
Vol 16 (7) ◽  
pp. 3765-3772 ◽  
Author(s):  
D Broccoli ◽  
L A Godley ◽  
L A Donehower ◽  
H E Varmus ◽  
T de Lange
Keyword(s):  
Cell Proliferation ◽  
Tumor Development ◽  
Mammary Tumorigenesis ◽  
Mammary Tumors ◽  
Mammary Glands ◽  
Telomerase Activity ◽  
Telomerase Rna ◽  
Proliferating Cells ◽  
Telomere Shortening ◽  
Mouse Mammary Tumors

Activation of telomerase in human cancers is thought to be necessary to overcome the progressive loss of telomeric DNA that accompanies proliferation of normal somatic cells. According to this model, telomerase provides a growth advantage to cells in which extensive terminal sequence loss threatens viability. To test these ideas, we have examined telomere dynamics and telomerase activation during mammary tumorigenesis in mice carrying a mouse mammary tumor virus long terminal repeat-driven Wnt-1 transgene. We also analyzed Wnt-1-induced mammary tumors in mice lacking p53 function. Normal mammary glands, hyperplastic mammary glands, and mammary carcinomas all had the long telomeres (20 to 50 kb) typical of Mus musculus and did not show telomere shortening during tumor development. Nevertheless, telomerase activity and the RNA component of the enzyme were consistently upregulated in Wnt-1-induced mammary tumors compared with normal and hyperplastic tissues. The upregulation of telomerase activity and RNA also occurred during tumorigenesis in p53-deficient mice. The expression of telomerase RNA correlated strongly with histone H4 mRNA in all normal tissues and tumors, indicating that the RNA component of telomerase is regulated with cell proliferation. Telomerase activity in the tumors was elevated to a greater extent than telomerase RNA, implying that the enzymatic activity of telomerase is regulated at additional levels. Our data suggest that the mechanism of telomerase activation in mouse mammary tumors is not linked to global loss of telomere function but involves multiple regulatory events including upregulation of telomerase RNA in proliferating cells.

Expression of Telomerase RNA, Telomerase Activity, and Telomere Length in Human Gliomas

1997 ◽  
Vol 239 (3) ◽  
pp. 830-834 ◽  
Author(s):  
Ken Morii ◽  
Ryuichi Tanaka ◽  
Kiyoshi Onda ◽  
Itaru Tsumanuma ◽  
Jyunichi Yoshimura
Keyword(s):  
Telomere Length ◽  
Telomerase Activity ◽  
Telomerase Rna ◽  
Human Gliomas

scholarly journals Telomerase Activity Reconstitutedin Vitrowith Purified Human Telomerase Reverse Transcriptase and Human Telomerase RNA Component

2000 ◽  
Vol 275 (29) ◽  
pp. 22568-22573 ◽  
Author(s):  
Kenkichi Masutomi ◽  
Shuichi Kaneko ◽  
Naoyuki Hayashi ◽  
Tatsuya Yamashita ◽  
Yukihiro Shirota ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Telomerase Activity ◽  
Telomerase Reverse Transcriptase ◽  
Telomerase Rna ◽  
Human Telomerase Reverse Transcriptase ◽  
Human Telomerase

A hypomorphic allele of telomerase uncovers the minimal functional length of telomeres in Arabidopsis

Genetics ◽  
2021 ◽  
Author(s):  
J Matthew Watson ◽  
Johanna Trieb ◽  
Martina Troestl ◽  
Kyle Renfrew ◽  
Terezie Mandakova ◽  
...  
Keyword(s):  
Genome Stability ◽  
Telomerase Activity ◽  
Minimal Length ◽  
Proper Function ◽  
Loop Formation ◽  
Telomeric Dna ◽  
Essential Requirement ◽  
Cis Acting ◽  
Hypomorphic Allele ◽  
Necessary And Sufficient

Abstract Despite the essential requirement of telomeric DNA for genome stability, the length of telomere tracts between species substantially differs, raising the question of the minimal length of telomeric DNA necessary for proper function. Here we address this question using a hypomorphic allele of the telomerase catalytic subunit, TERT. We show that although this construct partially restored telomerase activity to a tert mutant, telomeres continued to shorten over several generations, ultimately stabilizing at a bimodal size distribution. Telomeres on two chromosome arms were maintained at a length of 1kb, while the remaining telomeres were maintained at 400 bp. The longest telomeres identified in this background were also significantly longer in wild type populations, suggesting cis-acting elements on these arms either promote telomerase processivity or recruitment. Genetically disrupting telomerase processivity in this background resulted in immediate lethality. Thus, telomeres of 400 bp are both necessary and sufficient for Arabidopsis viability. As this length is the estimated minimal length for t-loop formation, our data suggest that telomeres long enough to form a t-loop constitute the minimal functional length.

Telomeres, telomerase, and apoptosis

2004 ◽  
Vol 82 (4) ◽  
pp. 498-507 ◽  
Author(s):  
Chiara Mondello ◽  
A Ivana Scovassi
Keyword(s):  
Cancer Cells ◽  
Telomerase Activity ◽  
Telomeric Dna ◽  
Apoptotic Response ◽  
Reverse Transcriptase Enzyme ◽  
Limited Life ◽  
Specific Proteins ◽  
Telomere Capping ◽  
The Impact ◽  
High Order Chromatin

Telomeres are specialized high-order chromatin structures that cap the ends of eukaryotic chromosomes. In vertebrates, telomeric DNA is composed of repetitions of the TTAGGG hexanucleotide, is bound to a set of specific proteins, and is elongated by the reverse transcriptase enzyme telomerase. Telomerase activity is promptly detected in cells with an indefinite replicative potential, such as cancer cells, while is almost undetectable in normal cells, which are characterized by a limited life span. Mounting evidence indicates that the maintenance of telomere integrity and telomerase protect cells from apoptosis. Disruption of the telomere capping function and (or) telomerase inhibition elicit an apoptotic response in cancer cells, while restoration of telomerase activity in somatic cells confers resistance to apoptosis. The possible mechanisms linking telomeres, telomerase and apoptosis are discussed in this review, together with the impact of this field in anticancer research.Key words: telomeres, telomerase, telomeric proteins, apoptosis, tumorigenesis.

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