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Updated: Apr 21, 2026
Generation of Cancer Cell Clones to Visualize Telomeric Repeat-containing RNA TERRA Expressed from a Single Telomere in Living Cells
Published on: January 17, 2019
Functional characterization of the TERRA transcriptome at damaged telomeres
Antonio Porro1, Sascha Feuerhahn1, Julien Delafontaine2
11] Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Life Sciences, 1015 Lausanne, Switzerland [2] Swiss Institute for Experimental Cancer Research (ISREC) at EPFL, Station 19, CH-1015 Lausanne, Switzerland.
Abstract:
Telomere deprotection occurs during tumorigenesis and aging upon telomere shortening or loss of the telomeric shelterin component TRF2. Deprotected telomeres undergo changes in chromatin structure and elicit a DNA damage response (DDR) that leads to cellular senescence. The telomeric long noncoding RNA TERRA has been implicated in modulating the structure and processing of deprotected telomeres. Here, we characterize the human TERRA transcriptome at normal and TRF2-depleted telomeres and demonstrate that TERRA upregulation is occurring upon depletion of TRF2 at all transcribed telomeres. TRF2 represses TERRA transcription through its homodimerization domain, which was previously shown to induce chromatin compaction and to prevent the early steps of DDR activation. We show that TERRA associates with SUV39H1 H3K9 histone methyltransferase, which promotes accumulation of H3K9me3 at damaged telomeres and end-to-end fusions. Altogether our data elucidate the TERRA landscape and defines critical roles for this RNA in the telomeric DNA damage response.
Insights
Telomere deprotection triggers cellular senescence. New research shows the long noncoding RNA TERRA interacts with SUV39H1, promoting DNA damage at telomeres and impacting cancer and aging.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Telomere deprotection, caused by telomere shortening or loss of TRF2, triggers a DNA damage response (DDR) leading to cellular senescence.
- The telomeric long noncoding RNA TERRA is involved in regulating the structure and processing of deprotected telomeres.
Purpose of the Study:
- To characterize the human TERRA transcriptome at normal and TRF2-depleted telomeres.
- To elucidate the role of TERRA in the telomeric DNA damage response.
Main Methods:
- Analysis of human TERRA transcriptome.
- TRF2 depletion experiments.
- Investigation of TERRA association with SUV39H1.
Main Results:
- TERRA is upregulated upon TRF2 depletion at all transcribed telomeres.
- TRF2 represses TERRA transcription via its homodimerization domain.
- TERRA associates with SUV39H1, promoting H3K9me3 accumulation at damaged telomeres and end-to-end fusions.
Conclusions:
- The study defines the TERRA landscape and its critical functions in the telomeric DNA damage response.
- TERRA plays a significant role in processes relevant to cancer and aging.
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