The human telomerase catalytic subunit and viral telomerase RNA reconstitute a functional telomerase complex in a cell-free system, but not in human cells

Trapp-Fragnet, Laëtitia; Marie-Egyptienne, Delphine T.; Fakhoury, Johans; Rasschaert, Denis; Autexier, Chantal

doi:10.2478/s11658-012-0031-6

Cited by 3 publications

(6 citation statements)

References 62 publications

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“…Further, TRs in land plants have a monophyletic origin [19]. This contradicts the previous paradigm, according to which relatively conserved TERT subunits associate with very diverse-and unrelated-RNAs [57,58].…”

Section: Rna Subunit Of Telomerasementioning

confidence: 84%

“…It was proposed that telomerase originated as an ancient reverse transcriptase (RT) that internalized a primitive template-bearing RNA during early eukaryotic evolution, and later evolved into modern telomerase ribonucleoproteins (RNPs) with various indispensable and stably TR-associated components [ 55 , 56 ]. In accordance with this notion, the TERT subunit has the ability to bind not exclusively the RNA molecule that provides the template sequence for DNA synthesis (TR), but also various non-telomeric sequences [ 57 , 58 ]. The conserved RT motifs between TERT and other RTs indicates that the TERT protein is closely related to RTs from the group of Penelope-like Elements (PLEs) and non-long-terminal-repeat (non-LTR) retrotransposons [ 55 ].…”

Section: The Origin Of Telomerasementioning

confidence: 99%

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Composition and Function of Telomerase—A Polymerase Associated with the Origin of Eukaryotes

Schrumpfová

Fajkus

2020

Biomolecules

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The canonical DNA polymerases involved in the replication of the genome are unable to fully replicate the physical ends of linear chromosomes, called telomeres. Chromosomal termini thus become shortened in each cell cycle. The maintenance of telomeres requires telomerase—a specific RNA-dependent DNA polymerase enzyme complex that carries its own RNA template and adds telomeric repeats to the ends of chromosomes using a reverse transcription mechanism. Both core subunits of telomerase—its catalytic telomerase reverse transcriptase (TERT) subunit and telomerase RNA (TR) component—were identified in quick succession in Tetrahymena more than 30 years ago. Since then, both telomerase subunits have been described in various organisms including yeasts, mammals, birds, reptiles and fish. Despite the fact that telomerase activity in plants was described 25 years ago and the TERT subunit four years later, a genuine plant TR has only recently been identified by our group. In this review, we focus on the structure, composition and function of telomerases. In addition, we discuss the origin and phylogenetic divergence of this unique RNA-dependent DNA polymerase as a witness of early eukaryotic evolution. Specifically, we discuss the latest information regarding the recently discovered TR component in plants, its conservation and its structural features.

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Section: Rna Subunit Of Telomerasementioning

confidence: 84%

Section: The Origin Of Telomerasementioning

confidence: 99%

Composition and Function of Telomerase—A Polymerase Associated with the Origin of Eukaryotes

Schrumpfová

Fajkus

2020

Biomolecules

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“…Thus, a single-strand overhang is produced. The common DNA polymerase then synthesizes the complementary strand after the dissociation of the telomerase holoenzyme [10][11][12][13][14]. This produces the telomere, a specialized DNA structure that gathers a plethora of proteins.…”

Section: Introductionmentioning

confidence: 99%

“…Many studies suggest that the minimal requirement for the normal activity of telomerase in vitro is the expression of both hTR and hTERT. However, the common belief is that the regulation and proper activity of telomerase in vivo is complex, multistep procedure that involves many other proteins as well [10][11][12][13]. When the telomere length reaches a critical point, the RNA component (hTR) provides the template and then the reverse transcriptase (hTERT) synthesizes DNA with its own RNA unit as the source.…”

Section: Introductionmentioning

confidence: 99%

Is there a connection between inflammation, telomerase activity and the transcriptional status of telomerase reverse transcriptase in renal failure?

Kordinas

Tsirpanlis

Nicolaou

et al. 2015

Cellular and Molecular Biology Letters

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Telomerase is involved in the elongation of telomeres. It remains active in very few types of cell in mature organisms. One such cell type is the lymphocytes. In this study, we investigated the activity and expression of telomerase in lymphocytes from renal failure patients and compared it to that for normal controls. Inflammation status was determined at the same time. The enzyme activity was measured using PCR-ELISA with peripheral blood mononuclear cells (PBMCs) from three groups: 53 healthy individuals, 50 patients with chronic kidney disease (CKD) and 50 dialysis patients. In the same cell populations, the expression of the reverse transcriptase of the human telomerase gene (hTERT) was measured via real-time PCR. The inflammationstatus of these individuals was determined by calculating the interleukin 6 (IL-6), IL-10, C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-a) serum concentrations via ELISA. The lowest levels of telomerase activity were detected in CKD, and this group had the highest IL-6 and CRP values and the lowest hTERT expression. The dialysis group showed significant differences in comparison to the normal subjects and to the CKD patients. Further studies are warranted in order to explore the way inflammation influences telomerase activity and hTERT expression.

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“…The secondary structures of vTR, cTR, and hTR are highly conserved, including the pseudoknot (core) domain that harbors the template sequence (CR-1) for the extension of telomeric repeats ( 15 ), the CR4-CR5 domain that is essential for proper assembly with TERT ( 15 ) and the H/ACA box and CR-7 domain, which are responsible for TR stability and localization ( 13 , 16 , 17 ). In addition, we showed that both vTR and hTR interact with chicken TERT and mediate telomerase activity in vitro ( 18 ). Therefore, we investigated whether overexpression of hTR could complement the loss of vTR in MDV-induced tumorigenesis and whether vTR possesses anti-apoptotic functions.…”

Section: Introductionmentioning

confidence: 99%

Viral and cellular telomerase RNAs possess host-specific anti-apoptotic functions

Kheimar,

Trapp-Fragnet,

Conradie

et al. 2023

Microbiol Spectr

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Human telomerase RNA (hTR) is overexpressed in many cancers and protects T cells from apoptosis in a telomerase-independent manner. The most prevalent cancer in the animal kingdom is caused by the highly oncogenic herpesvirus Marek’s disease virus (MDV). MDV encodes a viral telomerase RNA (vTR) that plays a crucial role in MDV-induced tumorigenesis and shares all four conserved functional domains with hTR. In this study, we assessed whether hTR drives tumor formation in this natural model of herpesvirus-induced tumorigenesis. Therefore, we replaced vTR with hTR in the genome of a highly oncogenic MDV. Furthermore, we investigated the anti-apoptotic activity of vTR, hTR, and their counterpart in the chicken [chicken telomerase RNA (cTR)]. hTR was efficiently expressed and did not alter replication of the recombinant virus. Despite its conserved structure, hTR did not complement the loss of vTR in virus-induced tumorigenesis. Strikingly, hTR did not inhibit apoptosis in chicken cells, but efficiently inhibited apoptosis in human cells. Inverse host restriction has been observed for vTR and cTR in human cells. Our data revealed that vTR, cTR, and hTR possess conserved but host-specific anti-apoptotic functions that likely contribute to MDV-induced tumorigenesis. IMPORTANCE hTR is overexpressed in many cancers and used as a cancer biomarker. However, the contribution of hTR to tumorigenesis remains elusive. In this study, we assessed the tumor-promoting properties of hTR using a natural virus/host model of herpesvirus-induced tumorigenesis. This avian herpesvirus encodes a telomerase RNA subunit (vTR) that plays a crucial role in viral tumorigenesis and shares all conserved functional domains with hTR. Our data revealed that vTR and cellular TRs of humans and chickens possess host-specific anti-apoptotic functions. This provides important translational insights into therapeutic strategies, as inhibition of apoptosis is crucial for tumorigenesis.

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The human telomerase catalytic subunit and viral telomerase RNA reconstitute a functional telomerase complex in a cell-free system, but not in human cells

Cited by 3 publications

References 62 publications

Composition and Function of Telomerase—A Polymerase Associated with the Origin of Eukaryotes

Composition and Function of Telomerase—A Polymerase Associated with the Origin of Eukaryotes

Is there a connection between inflammation, telomerase activity and the transcriptional status of telomerase reverse transcriptase in renal failure?

Viral and cellular telomerase RNAs possess host-specific anti-apoptotic functions

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