Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(21)

Published: May 6, 2021

Prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and recurrence PCR-positive tests have been widely reported in patients after recovery from COVID-19, but some these do not appear to shed infectious virus. We investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed integrated into DNA human cells culture transcription sequences might account for positive PCR seen patients. In support this hypothesis, we found copies genome infected cells. target site duplications flanking viral consensus LINE1 endonuclease recognition at integration sites, consistent with a retrotransposon-mediated, target-primed reverse retroposition mechanism. also found, patient-derived tissues, evidence suggesting large fraction is transcribed sequences, generating viral-host chimeric transcripts. The may thus contribute by infection clinical recovery. Because detected only subgenomic derived mainly 3' end host cell, virus cannot produced sequences.

Language: Английский

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Roles of transposable elements in the regulation of mammalian transcription

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(7), P. 481 - 497

Published: Feb. 28, 2022

Language: Английский

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Nanopore Sequencing Enables Comprehensive Transposable Element Epigenomic Profiling

Molecular Cell, Journal Year: 2020, Volume and Issue: 80(5), P. 915 - 928.e5

Published: Nov. 12, 2020

Language: Английский

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Identifying transposable element expression dynamics and heterogeneity during development at the single-cell level with a processing pipeline scTE

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: March 5, 2021

Abstract Transposable elements (TEs) make up a majority of typical eukaryote’s genome, and contribute to cell heterogeneity in unclear ways. Single-cell sequencing technologies are powerful tools explore cells, however analysis is typically gene-centric TE expression has not been addressed. Here, we develop single-cell processing pipeline, scTE, report the TEs single cells range biological contexts. Specific types expressed subpopulations embryonic stem dynamically regulated during pluripotency reprogramming, differentiation, embryogenesis. Unexpectedly, somatic including human disease-specific that undetectable bulk analyses. Finally, apply scTE ATAC-seq data, demonstrate can discriminate type using chromatin accessibly alone. Overall, our results classify dynamic patterns their contributions heterogeneity.

Language: Английский

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Taming transposable elements in vertebrates: from epigenetic silencing to domestication

Trends in Genetics, Journal Year: 2022, Volume and Issue: 38(6), P. 529 - 553

Published: March 17, 2022

Language: Английский

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Persistent circulation of soluble and extracellular vesicle‐linked Spike protein in individuals with postacute sequelae of COVID‐19

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(2)

Published: Feb. 1, 2023

ABSTRACT SARS‐CoV‐2, the causative agent of COVID‐19 disease, has resulted in death millions worldwide since beginning pandemic December 2019. While much progress been made to understand acute manifestations SARS‐CoV‐2 infection, less is known about post‐acute sequelae (PASC). We investigated levels both Spike protein (Spike) and viral RNA circulating patients hospitalized with without PASC. found that were more likely be present Among these patients, 30% positive for RNA; whereas, none individuals PASC both. The and/or PASC+ve increased or remained same as phase; PASC−ve group, components decreased totally absent. Additionally, this first report show part linked extracellular vesicles any presence vesicles. In conclusion, our findings suggest fragments persist recovered up 1 year longer after infection.

Language: Английский

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Amplifying gene expression with RNA-targeted therapeutics

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(7), P. 539 - 561

Published: May 30, 2023

Language: Английский

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Activation of human endogenous retroviruses and its physiological consequences

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 212 - 222

Published: Oct. 23, 2023

Language: Английский

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Towards targeting transposable elements for cancer therapy

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(2), P. 123 - 140

Published: Jan. 16, 2024

Language: Английский

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Locus-level L1 DNA methylation profiling reveals the epigenetic and transcriptional interplay between L1s and their integration sites

Cell Genomics, Journal Year: 2024, Volume and Issue: 4(2), P. 100498 - 100498

Published: Feb. 1, 2024

Long interspersed element 1 (L1) retrotransposons are implicated in human disease and evolution. Their global activity is repressed by DNA methylation, but deciphering the regulation of individual copies has been challenging. Here, we combine short- long-read sequencing to unveil L1 methylation heterogeneity across cell types, families, loci elucidate key principles involved. We find that youngest primate families specifically hypomethylated pluripotent stem cells placenta not most tumors. Locally, intronic intimately associated with gene transcription. Conversely, state can propagate proximal region up 300 bp. This phenomenon accompanied binding specific transcription factors, which drive expression chimeric transcripts. Finally, hypomethylation alone typically insufficient trigger due redundant silencing pathways. Our results illuminate epigenetic transcriptional interplay between their host genome.

Language: Английский

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