TERRA RNA Antagonizes ATRX and Protects Telomeres

@article{Chu2017TERRARA,
  title={TERRA RNA Antagonizes ATRX and Protects Telomeres},
  author={Hsueh-Ping Chu and Catherine Cifuentes-Rojas and Barry A. Kesner and Eric Aeby and Hun-Goo Lee and Chunyao Wei and Hyun Jung Oh and Myriam Boukhali and Wilhelm Haas and Jeannie T. Lee},
  journal={Cell},
  year={2017},
  volume={170},
  pages={86-101.e16}
}

Figures from this paper

PAR-TERRA is the main contributor to telomeric repeat-containing RNA transcripts in normal and cancer mouse cells.

TLDR
It is shown that PAR-TERRA molecules account for the majority of TERRA transcripts, displaying an increase of 2 to 4 orders of magnitude compared to the telomeric 18q transcript, and a large overlap between TERRA-interacting proteins in human and mouse cells is presented.

Characterization of telomeric repeat-containing RNA (TERRA) localization and protein interactions in primordial germ cells of the mouse†.

TLDR
The data indicate that TERRA expression and interactome during PGC development are regulated in a dynamic fashion that is dependent on gestational age and sex.

TERRA and the histone methyltransferase Dot1 cooperate to regulate senescence in budding yeast

TLDR
Evidence is provided that TERRA, a non-coding RNA transcribed from subtelomeres, contributes to senescence in yeast lacking telomerase (tlc1Δ), and data suggest that TERra and Dot1 cooperate to drive senescences.

RTEL1 influences the abundance and localization of TERRA RNA

TLDR
It is shown that the RTEL1 (Regulator of Telomere Length 1) helicase influences the abundance and localization of TERRA in human cells, and that loss of that function may contribute to the disease phenotypes of patients with RTel1 mutations.

Characterization of Telomeric Repeat-Containing RNA (TERRA) localization and protein interactions in Primordial Germ Cells of the mouse

TLDR
The results show that, TERRA interacting proteins are determined by sex in both PGCs and somatic cells, and indicate that TERRA expression and interactome during PGC development are regulated in a dynamic fashion that is dependent on gestational age and sex.

Induction and relocalization of telomeric repeat-containing RNAs during diauxic shift in budding yeast

TLDR
It is shown that TERRA expression is induced as yeast cells undergo diauxic shift, a lag phase during which yeast cells switch their metabolism from anaerobic fermentation to oxidative respiration, and this induction is transient as TERRA levels decrease during post-diaUXic shift.

CRISPR Cas13-based tools to track and manipulate endogenous telomeric repeat-containing RNAs in living cells

TLDR
A method to visualize TERRA in live cells via a combination of CRISPR Cas13 RNA labeling and Suntag technology and a chemically-induced protein dimerization system to manipulate TERRA subcellular localization in live Cells is developed.

CRISPR Cas13-Based Tools to Track and Manipulate Endogenous Telomeric Repeat-Containing RNAs in Live Cells

TLDR
A method to visualize TERRA in live cells via a combination of CRISPR Cas13 RNA labeling and SunTag technology and a chemically-induced protein dimerization system to manipulate TERRA subcellular localization in live Cells is developed.

Genomic origin and nuclear localization of TERRA telomeric repeat‐containing RNA: from Darkness to Dawn

TLDR
The studies on TERRA localization in the cell, its composition and some aspects of its transcriptional regulation are reviewed to summarize the current knowledge and controversies about the genomic origin of TERRA, with a focus on human and mouse TERRA.
...

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Novel mouse transcripts arising mainly from the subtelomere of chromosome 18, and to a lesser extend chromosome 9, are identified that resemble TERRA in several key aspects and are found to associate with nearly all chromosome ends and downregulation of the transcripts that originate from chromosome 18 causes a reduction in TERRA abundance.

TERRA Promotes Telomere Shortening through Exonuclease 1–Mediated Resection of Chromosome Ends

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TERRA transcription facilitates the 5′-3′ nuclease activity of Exo1 at chromosome ends, providing a means to regulate the telomere shortening rate and can regulate cellular lifespan through modulation of chromosome end processing activities.

TERRA transcripts are bound by a complex array of RNA-binding proteins.

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This study identifies a set of RNA-binding proteins, which endogenously bind and regulate TERRA in the context of primary mouse embryonic fibroblasts and predicts an impact of TERRA-associated RBPs on telomere biology and telomeres diseases, such as cancer and aging.

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Qualitative mass spectrometry-based proteomics identified new proteins involved in the homeostasis and telomeric abundance of TERRA, extending the knowledge ofTERRA regulation.

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The data identify TERRA as a telomerase ligand and natural direct inhibitor of human telomere substrate, which acts as a potent competitive inhibitor for telomeric DNA in addition to exerting an uncompetitive mode of inhibition.

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It is demonstrated that mammalian telomeres are transcribed into telomeric repeat–containing RNA (TERRA), and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity.

Molecular Dissection of Telomeric Repeat-Containing RNA Biogenesis Unveils the Presence of Distinct and Multiple Regulatory Pathways

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It is found that TERRA is regulated during the cell cycle, being lowest in late S phase and peaking in early G1, and the bulk of 3′-terminal UUAGGG repeats have an average length of 200 bases, indicating that the length heterogeneity of TERRA likely stems from its subtelomeric regions.

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It is proposed that defective telomere chromatinization through loss of ATRX promotes the persistence of aberrant DNA secondary structures, which in turn present a barrier to DNA replication, leading to replication fork stalling, collapse, HR and subsequent recombination-mediated telomeres synthesis in ALT cancers.
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