Telomeric repeat-containing RNA increases in aged human cells

Telomeric repeat-containing RNA (TERRA), transcribed from subtelomeric regions toward 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 region...

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Published inNucleic acids research Vol. 53; no. 13
Main Authors Hsieh, Yu-Hung, Tai, Chin-Hua, Yeh, Meng-Ting, Chen, Yu-Chen, Yang, Po-Cheng, Yen, Chien-Ping, Shen, Hong-Jhih, Yeh, Chan-Hsien, Kuo, Hung-Chih, Han, Der-Sheng, Chu, Hsueh-Ping Catherine
Format Journal Article
LanguageEnglish
Published England Oxford University Press 08.07.2025
Subjects
Aged
Aging - genetics
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Brain - metabolism
CCCTC-Binding Factor - genetics
Cell Differentiation - genetics
Cellular Senescence - genetics
Fibroblasts - metabolism
Genomics
Histones - metabolism
Humans
Promoter Regions, Genetic
Repetitive Sequences, Nucleic Acid
RNA - genetics
RNA-Seq
Single-Cell Analysis
Telomere - genetics
Transcription, Genetic
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Abstract Telomeric repeat-containing RNA (TERRA), transcribed from subtelomeric regions toward 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 reverse transcription quantitative polymerase chain reaction. 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.
AbstractList Telomeric repeat-containing RNA (TERRA), transcribed from subtelomeric regions toward 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 reverse transcription quantitative polymerase chain reaction. 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.
Telomeric repeat-containing RNA (TERRA), transcribed from subtelomeric regions toward 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 reverse transcription quantitative polymerase chain reaction. 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.Telomeric repeat-containing RNA (TERRA), transcribed from subtelomeric regions toward 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 reverse transcription quantitative polymerase chain reaction. 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.
Telomeric repeat-containing RNA (TERRA), transcribed from subtelomeric regions toward 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 reverse transcription quantitative polymerase chain reaction. 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. Graphical Abstract
Author Yeh, Chan-Hsien
Kuo, Hung-Chih
Hsieh, Yu-Hung
Chu, Hsueh-Ping Catherine
Yang, Po-Cheng
Yen, Chien-Ping
Shen, Hong-Jhih
Yeh, Meng-Ting
Han, Der-Sheng
Tai, Chin-Hua
Chen, Yu-Chen
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Snippet Telomeric repeat-containing RNA (TERRA), transcribed from subtelomeric regions toward telomeric ends, poses challenges in deciphering its complete sequences....
Telomeric repeat-containing RNA (TERRA), transcribed from subtelomeric regions toward telomeric ends, poses challenges in deciphering its complete sequences....
SourceID pubmedcentral
proquest
pubmed
crossref
SourceType Open Access Repository
Aggregation Database
Index Database
SubjectTerms Aged
Aging - genetics
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Brain - metabolism
CCCTC-Binding Factor - genetics
Cell Differentiation - genetics
Cellular Senescence - genetics
Fibroblasts - metabolism
Genomics
Histones - metabolism
Humans
Promoter Regions, Genetic
Repetitive Sequences, Nucleic Acid
RNA - genetics
RNA-Seq
Single-Cell Analysis
Telomere - genetics
Transcription, Genetic
Title Telomeric repeat-containing RNA increases in aged human cells
URI https://www.ncbi.nlm.nih.gov/pubmed/40637232
https://www.proquest.com/docview/3228829352
https://pubmed.ncbi.nlm.nih.gov/PMC12242772
Volume 53
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