Telomeric Repeat-Containing RNA Increases in Aged Human Cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1053332 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27227237_1.fastq.gz | Fastqsanger.gz | |||
| SRR27227238.fastq.gz | Fastqsanger.gz | |||
| SRR27227239_1.fastq.gz | Fastqsanger.gz | |||
| SRR27227239_2.fastq.gz | Fastqsanger.gz | |||
| SRR27227240_1.fastq.gz | Fastqsanger.gz |
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Project description:Telomeric repeat-containing RNA (TERRA), transcribed from subtelomeric regions towards telomeric ends, poses challenges in deciphering its complete sequences. Utilizing TERRA-capture RNA-seq and Oxford Nanopore direct RNA sequencing to acquire full-length TERRA, we annotate TERRA transcription regions in the human T2T-CHM13 reference genome. TERRA transcripts encompass hundreds to over a thousand nucleotides of telomeric repeats, predominantly originating from 61-29-37 bp repeat promoters enriched with H3K4me3, RNA pol II, CTCF, and R-loops. We develop a bioinformatics tool, TERRA-QUANT, for quantifying TERRA using RNA-seq datasets and find that TERRA increases with age in blood, brain, and fibroblasts. TERRA upregulation in aged leukocytes is confirmed by RT-qPCR. Single-cell RNA-seq analysis demonstrates TERRA expression across various cell types, with upregulation observed in neurons during human embryonic stem cell differentiation. Additionally, TERRA levels are elevated in brain cells in the early stage of Alzheimer’s disease. Our study provides evidence linking TERRA to human aging and diseases.
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Project description:ZBTB10 binds the telomeric variant repeat TTGGGG and interacts with TRF2
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Project description:The study of the proteins that bind to telomeric DNA in mammals has provided a deep understanding of the mechanisms of chromosome-end protection. However, very little is known on the binding of these proteins to nontelomeric DNA sequences. The TTAGGG DNA repeat proteins 1 and 2 (TRF1 and TRF2) bind to mammalian telomeres as part of the shelterin complex and are essential for maintaining chromosome end stability. In this study, we combined chromatin immunoprecipitation with high-throughput sequencing to map at high sensitivity and resolution, the human chromosomal sites to which TRF1 and TRF2 bind. While most of the identified sequences correspond to telomeric regions, we showed that these two proteins also bind to extratelomeric sites. The vast majority of these extra-telomeric sites contains interstitial telomeric sequences (or ITSs). However we also identified non-ITS sites, which are also satellite DNA but the ones mainly constitutive of centromeric and pericentromeric regions. Interestingly, the TRF-binding sites are often located in the proximity of genes or within introns. We propose that, by binding to extratelomeric sequences, TRF1 and TRF2 couple the functional state of telomeres to the long-range organization of chromosomes and gene regulation networks. ChIP-SEQ experiment of transformed human fibroblast BJ cells with 3 antibodies (1 monoclonal anti-TRF1, 1 monoclonal anti-TRF2, 1 polyclonal anti-TRF2) and a negative control (proteinG without antibody used as the ChIP background)
2011-05-03 | E-GEOD-26005 | biostudies-arrayexpress
Project description:Telomere is a highly refined system for maintaining the stability of linear chromosomes. Most telomeres rely on simple repetitive sequences and telomerase enzymes, but in some species or telomerase-defective situations, alternative telomere lengthening (ALT) mechanism is utilized to protect chromosomal ends. Telomere loss can induce telomere recombination by which specific sequences can be recruited into telomeres. However, canonical telomeric repeat-based telomeres have been found in mammals. Here, we show that mammalian telomeres can also be completely reconstituted using a non-telomeric unique sequence. We found that a specific subtelomeric element, named as mouse template for ALT (mTALT), is utilized for repairing telomeric DNA damage and composing new telomeric sequences in mouse embryonic stem cells. We found a high-level of non-coding mTALT transcript despite the heterochromatic nature of mTALT-based telomere. After ALT activation, the increased HMGN1, a non-histone chromosomal protein, contributed to maintaining telomere stability by regulating telomeric transcriptions. Our findings reveal novel molecular features of potential telomeric sequences which can reconstitute telomeres during cancer formation and evolution.
2020-07-17 | MSV000085772 | MassIVE
Project description:The study of the proteins that bind to telomeric DNA in mammals has provided a deep understanding of the mechanisms of chromosome-end protection. However, very little is known on the binding of these proteins to nontelomeric DNA sequences. The TTAGGG DNA repeat proteins 1 and 2 (TRF1 and TRF2) bind to mammalian telomeres as part of the shelterin complex and are essential for maintaining chromosome end stability. In this study, we combined chromatin immunoprecipitation with high-throughput sequencing to map at high sensitivity and resolution, the human chromosomal sites to which TRF1 and TRF2 bind. While most of the identified sequences correspond to telomeric regions, we showed that these two proteins also bind to extratelomeric sites. The vast majority of these extra-telomeric sites contains interstitial telomeric sequences (or ITSs). However we also identified non-ITS sites, which are also satellite DNA but the ones mainly constitutive of centromeric and pericentromeric regions. Interestingly, the TRF-binding sites are often located in the proximity of genes or within introns. We propose that, by binding to extratelomeric sequences, TRF1 and TRF2 couple the functional state of telomeres to the long-range organization of chromosomes and gene regulation networks.
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Project description:ZBTB10 binds the telomeric variant repeat TTGGGG and interacts with TRF2 [RNA-Seq]
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Project description:Sarcopenia is defined as aging-related loss of muscle mass and function. Telomere length in chromosomes shortens with age and is modulated by telomeric repeat-containing RNA (TERRA). This study aimed to explore the impact of aging and sarcopenia on telomere length and TERRA expression, and changes following strengthening exercise and nutrition intervention (supplement of branched-chain amino acids, calcium and vitamin D3) for 12 weeks in the sarcopenic population. Older adults (≥65 years old) were divided into non-sarcopenic controls (n = 36) and sarcopenic individuals (n = 36) after measurement of grip strength and body composition. The relative telomere length of leukocytes in all research participants was evaluated using the T/S ratio (telomere/single copy gene), and relative TERRA expression of leukocytes was determined by reverse-transcription qPCR (RT-qPCR). Generalized estimating equation (GEE) was used to analyze the influence of sarcopenia and intervention on the outcomes. There was no significant difference in telomere length between control subjects and participants with sarcopenia. TERRA expression was lower in sarcopenic participants compared to that in non-sarcopenic controls (5.18 ± 2.98 vs. 2.51 ± 1.89; p < 0.001). In the sarcopenic group, intervention significantly increased TERRA expression, but not telomere length. The GEE analysis demonstrated that TERRA expression was negatively associated with sarcopenia (β coefficient = -2.705, p < 0.001) but positively associated with intervention (β coefficient = 1.599, p = 0.023). Sarcopenia is associated with a decrease in TERRA expression in leukocytes. Rebound TERRA expression (returning to the level similar to the non-sarcopenic controls) was observed in the sarcopenic group after exercise and nutrition intervention. Future studies are warranted to examine the potential of TERRA as a biomarker for sarcopenia and its subsequent responses to intervention.
| S-EPMC7762552 | biostudies-literature
Project description:Telomeric repeat-containing RNA (referred to as TERRA), a noncoding RNA molecule, has recently been found in mammalian cells. The detailed structural features and function of the TERRA RNA at human chromosome ends remain unclear, although this RNA molecule may be a key component of the telomere machinery. In the present studies, we investigated the structural features of human TERRA RNA in living cells. Using a light-switching pyrene probe, we found that human TERRA RNA forms a parallel G-quadruplex structure in living cells, providing the in vivo evidence for the presence of the G-quadruplex in human TERRA RNA. Furthermore, imaging experiments clearly show that TERRA RNA G-quadruplex localizes to telomere DNA at cell nuclei. These results provide valuable information to allow understanding of the structure and function of human TERRA RNA.
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Project description:Ribosome Profiling Reveals Novel Regulation of C9ORF72 GGGGCC Repeat-Containing RNA Translation
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Project description:TERRA (telomeric repeat-containing RNA) is a class of long noncoding RNAs transcribed from subtelomeric and telomeric regions. TERRA binds to the subtelomeric and telomeric DNA-forming R-loops (DNA-RNA hybrids), which are involved in telomere maintenance and telomerase function, but the role of TERRA in human cells is not well characterized. Here, we comprehensively investigated for the first time TERRA expression in primary human hematopoietic cells from an exploratory cohort of patients with acute myeloid leukemia (AML), patients with acute lymphoblastic leukemia (ALL), patients with telomere biology disorder (TBD), and healthy subjects. TERRA expression was repressed in primary human hematopoietic cells, including healthy donors, patients with ALL, and patients with TBD, irrespective of their telomere length, except for AML. A second cohort comprising 88 patients with AML showed that TERRA was overexpressed in an AML subgroup also characterized by higher R-loop formation, low TERT and RNAseH2 expression, and a paucity of somatic splicing factor mutations. Telomere length did not correlate with TERRA expression levels. To assess the role of TERRA R-loops in AML, we induced R-loop depletion by increasing RNAseH1 expression in 2 AML cell lines. Decreased TERRA R-loops in AML cell lines resulted in increased chemosensitivity to cytarabine. Our findings indicate that TERRA is uniformly repressed in primary human hematopoietic cells but abnormally expressed in an AML subset with low telomerase.
| S-EPMC10694524 | biostudies-literature