Human telomerase reverse transcriptase binds to a pre-organized hTR<i>in vivo</i>exposing its template

Zemora, Georgeta; Handl, Stefan; Waldsich, Christina

doi:10.1093/nar/gkv1065

Cited by 17 publications

(34 citation statements)

References 51 publications

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“…SHAPE analysis supports pseudoknot folding for S. cerevisiae and human TER t/PK [52]. A recent study using in vivo chemical probing (DMS) also apparently showed that the pseudoknot does form in the protein-free human TER, but the template is sequestered and becomes more exposed on TERT binding [53]. However, the chemical probing data may be equally consistent with the alternative model for free human TER discussed above.…”

Section: Ter Structure and Assembly With Tertmentioning

confidence: 80%

Structural biology of telomerase and its interaction at telomeres

Wang

Feigon

2017

Current Opinion in Structural Biology

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Telomerase is an RNP that synthesizes the 3′ ends of linear chromosomes and is an important regulator of telomere length. It contains a single long non-coding telomerase RNA (TER), telomerase reverse transcriptase (TERT), and other proteins that vary among organisms. Recent progress in structural biology of telomerase includes reports of the first cryo-electron microscopy structure of telomerase, from Tetrahymena, new crystal structures of TERT domains, telomerase RNA structures and models, and identification in Tetrahymena telomerase holoenzyme of human homologues of telomere-associated proteins that have provided a more unified view of telomerase interaction at telomeres as well as insights into the role of telomerase RNA in activity and assembly.

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Section: Ter Structure and Assembly With Tertmentioning

confidence: 80%

Structural biology of telomerase and its interaction at telomeres

Wang

Feigon

2017

Current Opinion in Structural Biology

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“…Terc-sRNA has a second target site on TERC RNA (positions 12-31), spanning the TBE region located at the 5' of the template region. In vertebrates, TBE consists of a long-range base-paired region known as P1 helix [36,100], which physically prevents TERT from reverse transcribing flanking non-template regions. Otherwise, nontelomeric DNA is synthetized at chromosome ends, inhibiting the binding of telomeric protein and resulting in detrimental effects for telomerase function [101].…”

Section: Terc-interacting Proteins: the Usual And Unusual Suspectsmentioning

confidence: 99%

How RNAi machinery enters the world of telomerase

2019

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Human telomerase holoenzyme consists of the catalytic component TERT and the template RNA TERC. However, a network of accessory proteins plays key roles in its assembly, localization and stability. Defects in genes involved in telomerase biology affect the renewal of critical stem cell populations and cause disorders such as telomeropathies. Moreover, activation of telomerase in somatic cells allows neoplastic cells to proliferate indefinitely, thus contributing to tumorigenesis. For these reasons, identification of new players involved in telomerase regulation is crucial for the determination of novel therapeutic targets and biomarkers. In the very last years, increasing evidence describes components of the RNAi machinery as a new layer of complexity in human telomerase activity. In this review, we will discuss how AGO2 and other proteins which collaborate with AGO2 in RNAi pathway play a pivotal role in TERC stability and function. ARTICLE HISTORY

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“…This interaction is facilitated by TER-TERT interactions, which expose the TER template. 19 However, telomerase substrate affinity is not necessarily dependent on the extent of telomeric DNA:TER RNA base pairing. 20 Typically, the last third of the template binds to telomeric DNA, although the Saccharomyces cerevisiae TER utilizes multiple telomeretemplate alignments.…”

Section: Ter Templatementioning

confidence: 99%

Telomerase RNA is more than a DNA template

Webb

Zakian

2016

RNA Biology

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The addition of telomeric DNA to chromosome ends is an essential cellular activity that compensates for the loss of genomic DNA that is due to the inability of the conventional DNA replication apparatus to duplicate the entire chromosome. The telomerase reverse transcriptase and its associated RNA bind to the very end of the telomere via a sequence in the RNA and specific protein-protein interactions. Telomerase RNA also provides the template for addition of new telomeric repeats by the reverse-transcriptase protein subunit. In addition to the template, there are 3 other conserved regions in telomerase RNA that are essential for normal telomerase activity. Here we briefly review the conserved core regions of telomerase RNA and then focus on a recent study in fission yeast that determined the function of another conserved region in telomerase RNA called the Stem Terminus Element (STE). (1) The STE is distant from the templating core of telomerase in both the linear and RNA secondary structure, but, nonetheless, affects the fidelity of telomere sequence addition and, in turn, the ability of telomere binding proteins to bind and protect chromosome ends. We will discuss possible mechanisms of STE action and the suitability of the STE as an anti-cancer target.

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Human telomerase reverse transcriptase binds to a pre-organized hTRin vivoexposing its template

Cited by 17 publications

References 51 publications

Structural biology of telomerase and its interaction at telomeres

Structural biology of telomerase and its interaction at telomeres

How RNAi machinery enters the world of telomerase

Telomerase RNA is more than a DNA template

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