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Updated: Jun 25, 2025
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Ultra-long Read Sequencing for Whole Genomic DNA Analysis
Published on: March 15, 2019
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TERRA ONTseq: a long-read-based sequencing pipeline to study the human telomeric transcriptome.
Joana Rodrigues1, Roberta Alfieri2,3, Silvia Bione2
1Instituto de Medicina Molecular João Lobo Antunes (iMM), Faculdade de Medicina da Universidade de Lisboa, Lisbon 1649-028, Portugal.
RNA (New York, N.Y.)
|May 22, 2024
Summary
A new sequencing method reveals that most human telomeres produce long noncoding RNA TERRA. This method also identified novel TERRA transcription start sites and promoters, offering a clearer view of TERRA biogenesis.
Area of Science:
- Molecular Biology
- Genomics
- Epigenetics
Background:
- Long noncoding RNA TERRA is transcribed from telomeres in eukaryotes.
- Human TERRA transcription is partly regulated by CpG-rich promoters in subtelomeres.
- Previous methods for analyzing TERRA expression provided incomplete and biased data.
Purpose of the Study:
- To develop and apply a novel long-read sequencing pipeline, TERRA ONTseq, for comprehensive human TERRA analysis.
- To investigate the extent of TERRA production across human telomeres.
- To identify TERRA transcription start sites (TSSs) and promoters in human subtelomeres.
Main Methods:
- Development of a novel long-read sequencing pipeline (TERRA ONTseq).
- Application of TERRA ONTseq to various human cell lines.
- Bioinformatic analysis of sequencing data to identify TERRA transcripts, TSSs, and promoter regions.
Main Results:
- TERRA ONTseq demonstrated that the vast majority of human telomeres produce TERRA.
- TERRA transcript levels vary significantly depending on the chromosome of origin.
- TERRA TSS regions were identified in over half of human subtelomeres, often near 29 bp repeat sequences.
- A novel TERRA promoter was isolated from the subtelomere of Chromosome 7.
Conclusions:
- TERRA ONTseq provides a refined understanding of human TERRA biogenesis and expression.
- The study reveals a broader distribution of 29 bp repeat-related sequences involved in TERRA transcription than previously thought.
- TERRA ONTseq is a valuable new tool for future research on TERRA and telomere biology.
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