Functional Characterization of the TERRA Transcriptome at Damaged Telomeres

Overview

Journal Nat Commun

Specialty Biology

Date 2014 Nov 1

PMID 25359189

Citations 134

Authors

Antonio Porro

Sascha Feuerhahn

Julien Delafontaine

Harold Riethman

Jacques Rougemont

Joachim Lingner

Affiliations

Soon will be listed here.

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.

Citing Articles

Elevated Telomeric Repeat-Containing RNA (TERRA) Levels Linked to Telomere Dysfunction and Telomerase Inactivity in Blood Cells of Children With Aplastic Anemia.

Mazumdar J, Chowdhury P, Mondal B, Kumar Das A, Ghosh U Cureus. 2024; 16(10):e71241.

PMID: 39525171 PMC: 11550455. DOI: 10.7759/cureus.71241.

Elucidation of the molecular mechanism of the breakage-fusion-bridge (BFB) cycle using a CRISPR-dCas9 cellular model.

Singh M, Raseley K, Perez A, MacKenzie D, Kosiyatrakul S, Desai S Nucleic Acids Res. 2024; 52(19):11689-11703.

PMID: 39193906 PMC: 11514482. DOI: 10.1093/nar/gkae747.

TERRA transcripts localize at long telomeres to regulate telomerase access to chromosome ends.

Bettin N, Querido E, Gialdini I, Grupelli G, Goretti E, Cantarelli M Sci Adv. 2024; 10(24):eadk4387.

PMID: 38865460 PMC: 11168465. DOI: 10.1126/sciadv.adk4387.

TERRA ONTseq: a long-read-based sequencing pipeline to study the human telomeric transcriptome.

Rodrigues J, Alfieri R, Bione S, Azzalin C RNA. 2024; 30(8):955-966.

PMID: 38777382 PMC: 11251519. DOI: 10.1261/rna.079906.123.

TERRA-LSD1 phase separation promotes R-loop formation for telomere maintenance in ALT cancer cells.

Xu M, Senanayaka D, Zhao R, Chigumira T, Tripathi A, Tones J Nat Commun. 2024; 15(1):2165.

PMID: 38461301 PMC: 10925046. DOI: 10.1038/s41467-024-46509-z.

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