Telomeric repeat-containing RNA increases in aged human cells
Journal
Nucleic Acids Research
Journal Volume
53
Journal Issue
13
Start Page
gkaf597
ISSN
0305-1048
1362-4962
Date Issued
2025-07-22
Author(s)
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
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.
Publisher
Oxford University Press (OUP)
Type
journal article