TE-Seq: A Transposable Element Annotation and RNA-Seq Pipeline DOI Creative Commons
Maxfield M. G. Kelsey, Radha L. Kalekar, John M. Sedivy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Abstract Motivation The recognition that transposable elements (TEs) play important roles in many biological processes has elicited growing interest analyzing sequencing data derived from this ‘dark genome’. This is however complicated by the highly repetitive nature of these sequences genomes, requiring deployment several problem-specific tools as well curation appropriate genome annotations. pipeline aims to make analysis TE and their expression more generally accessible. Results TE-Seq conducts an end-to-end RNA data, examining both genes TEs. It implements most current computational methods tailor- made for TEs, produces a comprehensive at level individual element clade level. Furthermore, if supplied with long-read DNA it able assess non-reference (polymorphic) loci. As demonstration, we analyzed proliferating, early senescent, late senescent lung fibroblast RNA-Seq created custom reference annotations cell strain using Nanopore data. We found retrotransposable (RTE) clades were upregulated senescence, which included non-reference, intact, potentially active elements. Availability implementation available Snakemake can be obtained https://github.com/maxfieldk/TE-Seq . All software dependencies besides Docker/Singularity are packaged into container automatically built deployed runtime.

Language: Английский

CRISPR-Enabled Autonomous Transposable Element (CREATE) for RNA-based gene editing and delivery DOI
Yuxiao Wang, Ruei‐Zeng Lin, Meghan T. Harris

et al.

EMBO Reports, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

Citations

1
Research progress and applications of epigenetic biomarkers in cancer DOI Creative Commons
Jianjun Gao, Wujiang Shi,

Jiangang Wang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 12, 2024

Epigenetic changes are heritable in gene expression without the nucleotide sequence of genes. play an important role development cancer and process malignancy metastasis. Previous studies have shown that abnormal epigenetic can be used as biomarkers for disease status prediction. The reversibility controllability modification also provide new strategies early prevention treatment. In addition, corresponding drug has reached clinical stage. this paper, we will discuss recent progress application tumor from three perspectives: DNA methylation, non-coding RNA, histone modification, order to opportunities additional research applications.

Language: Английский

Citations

5
RNA and condensates: Disease implications and therapeutic opportunities DOI Creative Commons

Tina W. Han,

Bede Portz,

Richard A. Young

et al.

Cell chemical biology, Journal Year: 2024, Volume and Issue: 31(9), P. 1593 - 1609

Published: Sept. 1, 2024

Language: Английский

Citations

5
p53 mediated regulation of LINE1 retrotransposon derived R-loops DOI Creative Commons

Pratyashaa Paul,

Arun Kumar,

Ankita Subhadarsani Parida

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108200 - 108200

Published: Jan. 1, 2025

Language: Английский

Citations

0
Mangiferin Protects Mesenchymal Stem Cells Against DNA Damage and Cellular Aging via SIRT1 Activation DOI
Gyeong Min Lim, Gwang-Won Cho

Mechanisms of Ageing and Development, Journal Year: 2025, Volume and Issue: unknown, P. 112038 - 112038

Published: Jan. 1, 2025

Language: Английский

Citations

0
Comparative Genomics Reveals LINE-1 Recombination with Diverse RNAs DOI Creative Commons
Cheuk‐Ting Law, Kathleen H. Burns

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

ABSTRACT Long interspersed element-1 (LINE-1, L1) retrotransposons are the most abundant protein-coding transposable elements (TE) in mammalian genomes, and have shaped genome content over 170 million years of evolution. LINE-1 is self-propagating mobilizes other sequences, including Alu elements. Occasionally, forms chimeric insertions with non-coding RNAs mRNAs. U6 spliceosomal small nuclear RNA/LINE-1 chimeras best known, though there no comprehensive catalogs chimeras. To address this, we developed TiMEstamp, a computational pipeline that leverages multiple sequence alignments (MSA) to estimate age identify candidate where an adjacent arrives contemporaneously. Candidates were refined by detecting hallmark features L1 retrotransposition, such as target site duplication (TSD). Applying this human genome, recovered all known species discovered new involving RNAs, elements, mRNA fragments. Some compatible mechanisms, RNA ligation. Other structures nominate novel trans-splicing. We also see evidence loci defunct promoters can acquire regulatory from nearby genes restore retrotransposition activity. These discoveries highlight recombinatory potential implications for evolution TE domestication. GRAPHICAL

Language: Английский

Citations

0
Targeted detection of endogenous LINE-1 proteins and ORF2p interactions DOI Creative Commons
Mathias I. Nielsen, Justina C. Wolters,

Omar G. Rosas Bringas

et al.

Mobile DNA, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 6, 2025

Both the expression and activities of LINE-1 (L1) retrotransposons are known to occur in numerous cell-types implicated pathobiological contexts such as aging-related inflammation, autoimmunity, cancers. L1s encode two proteins that translated from bicistronic transcripts. The translation product ORF1 (ORF1p) has been robustly detected by immunoassays shotgun mass spectrometry (MS). Yet, more sensitive detection methods would enhance use ORF1p a clinical biomarker. In contrast, until now, no direct evidence endogenous L1 ORF2 protein (ORF2p) shown. Instead, assays for ORF2p have limited ectopic ORF over-expression indirect enzymatic activity, sequencing de novo genomic insertions. Immunoassays problematic, producing apparent false positives due cross-reactivities, MS not yielded reliable peptides biological samples. Here we present targeted assays, selected parallel reaction monitoring (SRM PRM, respectively) detect quantify at their abundances. We were able our samples down range low attomoles. Confident ability affinity enrich ORF2p, describe an interactome associated with ORF2-containing macromolecular assemblies. This is first assay demonstrate robust quantitation ORF2p. directly quantitatively will improve understanding developmental diseased cell states where its activity naturally occur. simultaneously important step forward analytical biochemistry. Endogenous interactomes can now be presented confidence among enriched proteins.

Language: Английский

Citations

0
The domesticated transposon protein L1TD1 associates with its ancestor L1 ORF1p to promote LINE-1 retrotransposition DOI Open Access
Gülnihal Kavaklıoğlu, Alexandra Podhornik, Terezia Vcelkova

et al.

Published: Feb. 17, 2025

Repression of retrotransposition is crucial for the successful fitness a mammalian organism. The domesticated transposon protein L1TD1, derived from LINE-1 (L1) ORF1p, an RNA-binding that expressed only in some cancers and early embryogenesis. In human embryonic stem cells, it found to be essential maintaining pluripotency. cancer, L1TD1 expression highly correlative with malignancy progression as such considered potential prognostic factor tumors. However, its molecular role cancer remains largely unknown. Our findings reveal DNA hypomethylation induces HAP1 tumor cells. depletion significantly modulates both proteome transcriptome thereby reduces cell viability. Notably, associates L1 transcripts interacts ORF1p protein, facilitating retrotransposition. data suggest collaborates ancestral RNA chaperone, ensuring efficient retrotransposons, rather than directly impacting abundance targets. this way, might have important not during development but also tumorigenesis.

Language: Английский

Citations

0
RNA Transcripts Serve as a Template for Double-Strand Break Repair in Human Cells DOI Open Access
Manisha Jalan, Alessandra Brambati, Hina Shah

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Double-strand breaks (DSBs) are toxic lesions that lead to genome instability. While canonical DSB repair pathways typically operate independently of RNA, emerging evidence suggests RNA:DNA hybrids and transcripts near damaged sites can influence outcomes. However, a direct role for transcript RNA as template during in human cells is yet be established. In this study, we designed fluorescent- sequencing-based assays, which demonstrated RNA-containing oligonucleotides messenger serve templates promote repair. We conducted CRISPR/Cas9-based genetic screen identify factors RNA-templated (RT-DSBR), the candidate polymerases, identified DNA polymerase-zeta (Polζ) potential reverse transcriptase facilitates RT-DSBR. Furthermore, by analyzing sequencing data from cancer genomes, presence whole intron deletions, unique genomic scar reflective RT-DSBR activity generated when spliced mRNA serves template. These findings highlight an alternative pathway repairing DSBs transcribed genes, with mutagenic consequences.

Language: Английский

Citations

0
LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker DOI Creative Commons
Pamela Santiago, Sho Sato, Stephanie J. Zhang

et al.

npj Precision Oncology, Journal Year: 2025, Volume and Issue: 9(1)

Published: March 6, 2025

Long interspersed element 1 (LINE-1) retrotransposons are repetitive sequences that can move within the genome by an autonomous mechanism. To limit their mutagenic potential, benign cells restrict LINE-1 expression through molecular mechanisms such as DNA methylation and histone modification, but these usually impaired in cancer. Clear cell ovarian carcinoma (CCOC) represents 5-10% of cancers is thought to arise from endometriosis. Women with advanced CCOC face poor prognoses, highlighting importance understanding early disease pathogenesis. In our study, 33 40 cases (over 82%) tumors express ORF1p, a LINE-1-encoded protein. We found de-repression event CCOC, ORF1p enhanced during transition typical atypical endometriosis persists invasive Finally, using single-molecule array (Simoa) assays, we detected patient blood, suggesting it potential minimally biomarker for this disease.

Language: Английский

Citations

0