An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity

Gazzaniga, Francesca S.; Blackburn, Elizabeth H.

doi:10.1182/blood-2014-06-582254

Cited by 67 publications

(86 citation statements)

References 49 publications

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“…Increasing evidence suggests that lncRNAs may function as pro-apoptotic or anti-apoptotic regulators [22]. They are frequently dysregulated in various disease models [23].…”

Section: Discussionmentioning

confidence: 99%

Long Non Coding RNA-UCA1 Contributes to Cardiomyocyte Apoptosis by Suppression of p27 Expression

Liu

Daliang(²,

et al. 2015

Cell Physiol Biochem

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This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Key WordsLong non coding RNA • UCA1 • Cardiomyocyte apoptosis • p27 Abstract Background/Aims: Urothelial carcinoma-associated 1 (UCA1) is a recently identified long non coding RNA (lncRNA). However, few studies have explored its role in cardiomyocytes after focal cardiac ischemia reperfusion injury (CIR). Methods: Rat CIR models were established using ligation of the Lower Anterior Descending artery (LAD). Cell apoptosis and reactive oxygen species (ROS) production in cardiac tissues were explored using immunohistochemistry and DHE staining. lncRNA expression patterns were detected using microarray and validated by qPCR. Cell viability and apoptosis were examined using MTT assay and flow cytometry. Results: CIR significantly induced cell apoptosis and ROS production in the rat model. The results of microarray demonstrated the reduced expression of UCA1, which was validated by qPCR. Follow-up experiments showed that UCA1 was involved in H 2 O 2 -induced cell apoptosis. We further showed that UCA1 negatively correlated with the expression of p27. Moreover, overexpression of p27 could induce primary cardiomyocyte apoptosis. Conclusions: Reduction of UCA1 levels plays a pro-apoptotic role in primary cardiomyocytes partially through stimulation of p27 protein expression. These results are in agreement with the observed levels of UCA1, p27 and apoptosis after cardiac I/R injury, suggesting that UCA1 might have an important role during I/R injury.

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“…Increasing evidence suggests that lncRNAs may function as pro-apoptotic or anti-apoptotic regulators [22]. They are frequently dysregulated in various disease models [23].…”

Section: Discussionmentioning

confidence: 99%

Long Non Coding RNA-UCA1 Contributes to Cardiomyocyte Apoptosis by Suppression of p27 Expression

Liu

Daliang(²,

et al. 2015

Cell Physiol Biochem

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“…It is impossible to completely exclude pleiotropic effects, and, indeed, TERT has nontelomeric functions in the cell related to mitochondria function and oxidative stress that may be important in ischemic heart disease (32,33 ). Also, TERC overexpression has a possible antiapoptotic role in CD4 T cells, independent of TERT and telomere integrity (34 ). OBFC1, which is part of the CST complex, might have extratelomeric functions and a function in DNA repair; however, the various functions of CST complexes in humans are not well known (35 ).…”

Section: Figmentioning

confidence: 99%

Short Telomere Length and Ischemic Heart Disease: Observational and Genetic Studies in 290 022 Individuals

et al. 2016

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BACKGROUND: Short telomeres are associated with aging and have been associated with a high risk of ischemic heart disease in observational studies; however, the latter association could be due to residual confounding and/or reverse causation. We wanted to test the hypothesis that short telomeres are associated with high risk of ischemic heart disease using a Mendelian randomization approach free of reverse causation and of most confounding.

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“…TERC was previously shown to possess an anti-apoptotic role in human immune cells independent of its function in telomerase activity [21]. To test the biological function of the alTERC in the motor neurons cells we examined the effect of overexpression of alTERC and the canonical mTERC on cell survival following exposure to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Expression of functional alternative telomerase RNA component gene in mouse brain and in motor neurons cells protects from oxidative stress

et al. 2016

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Telomerase, a ribonucleoprotein, is highly expressed and active in many tumor cells and types, therefore it is considered to be a target for anti-cancer agents. On the other hand, recent studies demonstrated that activation of telomerase is a potential therapeutic target for age related diseases. Telomerase mainly consists of a catalytic protein subunit with a reverse transcription activity (TERT) and an RNA component (TERC), a long non-coding RNA, which serves as a template for the re-elongation of telomeres by TERT. We previously showed that TERT is highly expressed in distinct neuronal cells of the mouse brain and its expression declined with age. To understand the role of telomerase in non-mitotic, fully differentiated cells such neurons we here examined the expression of the other component, TERC, in mouse brain. Surprisingly, by first using bioinformatics analysis, we identified an alternative TERC gene (alTERC) in the mouse genome. Using further experimental approaches we described the presence of a functional alTERC in the mouse brain and spleen, in cultures of motor neurons- like cells and neuroblastoma tumor cells. The alTERC is similar (87%) to mouse TERC (mTERC) with a deletion of 18 bp in the TERC conserved region 4 (CR4). This alTERC gene is expressed and its product interacts with the endogenous mTERT protein and with an exogenous human TERT protein (hTERT) to form an active enzyme. Overexpression of the alTERC and the mTERC genes, in mouse motor neurons like cells, increased the activity of TERT without affecting its protein level. Under oxidative stress conditions, alTERC significantly increased the survival of motor neurons cells without altering the level of TERT protein or its activity.The results suggest that the expression of the alTERC gene in the mouse brain provides an additional way for regulating telomerase activity under normal and stress conditions and confers protection to neuronal cells from oxidative stress.

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An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity

Cited by 67 publications

References 49 publications

Long Non Coding RNA-UCA1 Contributes to Cardiomyocyte Apoptosis by Suppression of p27 Expression

Long Non Coding RNA-UCA1 Contributes to Cardiomyocyte Apoptosis by Suppression of p27 Expression

Short Telomere Length and Ischemic Heart Disease: Observational and Genetic Studies in 290 022 Individuals

Expression of functional alternative telomerase RNA component gene in mouse brain and in motor neurons cells protects from oxidative stress

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