Human Endogenous Retroviruses and Their Putative Role in Pathogenesis of Alzheimer’s Disease, Inflammation, and Senescence DOI Creative Commons

Patrycja Kozubek,

Julia Kuźniar,

Magdalena Czaja

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 13(1), P. 59 - 59

Published: Dec. 30, 2024

The human endogenous retroviruses (HERVs) are ancient exogenous that were embedded in the germline over 30 million years ago and underwent an endogenization process. They make up roughly 8% of genome. HERVs exhibit many physiological non-physiological functions; for example, they play a role development diseases. have been shown to affect carcinogenesis by modifying expression host genes through their functions as enhancers promoters. Additionally, some molecules derived from may stimulate immune system. Recently research has focused on effect neurodegenerative diseases, including Alzheimer’s disease (AD), which is most common cause dementia. AD also linked significant deterioration quality life. article aims highlight potential diseases such senescence. Moreover, it estimated be targets diagnosis therapy AD.

Language: Английский

Endogenous retroviruses in neurodevelopmental, psychotic and cognitive disorders DOI Creative Commons
Urs Meyer, Iris‐Katharina Penner

Microbes and Infection, Journal Year: 2025, Volume and Issue: unknown, P. 105479 - 105479

Published: Feb. 1, 2025

Endogenous retroviruses (ERVs) are inherited retroviral genomic elements that integrated into the mammalian genome through germline infections and insertions during evolution. Human ERVs (HERVs) comprise approximately 8% of human increasingly recognized to be involved in etiology pathophysiology numerous brain disorders. In this narrative review, we summarize existing evidence linking abnormal HERV expression neurodevelopmental psychosis-related disorders discuss how these may contribute heterogeneity clinical outcomes. We also review findings suggesting aberrant late-onset cognitive with neurodegenerative components, such as Alzheimer's disease (AD) other forms dementia. conclude implicating neurodevelopmental, psychotic, is manifold stems from diverse research fields, including post-mortem studies, serological investigations, gene analyses, trials HERV-specific pharmacological compounds. The recent establishment use animal models offer a complementary experimental platform will help establish causal relationships identify specific pathways affected by expression. Yet, significant gaps persist understanding role HERVs disorders, particularly concerning specificity stability conditions. Addressing unresolved questions appears crucial for optimizing potential benefits therapeutic interventions aimed at targeting across broad spectrum HERV-associated CNS

Language: Английский

Citations

1
Retrotrans-genomics identifies aberrant THE1B endogenous retrovirus fusion transcripts in the pathogenesis of sarcoidosis DOI Creative Commons
Shunsuke Funaguma, Aritoshi Iida, Yoshihiko Saito

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

Transposon-like human element 1B (THE1B) originates from ancient retroviral sequences integrated into the primate genome approximately 50 million years ago, now accounting for at least 27,233 copies in genome, suggesting their extensive influence on genomic architecture. Here we report identification of 19 THE1B fusion transcripts through short- and long-read RNA-seq analysis, 15 which are previously unmapped, showing elevated expression 16 individuals with sarcoid myopathy (SM), as compared to 400 controls various other muscle diseases. Analysis publicly available data indicated a correlation between reduced eight clinical improvement cutaneous sarcoidosis receiving tofacitinib treatment. Single-cell or single-nucleus analyses not only confirmed these but also revealed novel read-through transcript, SIRPB1-SIRPD, TREM2.1, predominantly granuloma-associated macrophages. The profiles tuberculosis (TB) significantly differed SM single-cell data, that differences TB's caseous granulomas sarcoidosis's non-caseous might be linked disparate patterns transcripts. Our retrotrans-genomics approach has identified landscape provided new insights its etiology. Sarcoidosis is an inflammatory systemic disorder characterized by developed epithelioid cells organs. Here, authors identify endogenous retrovirus aberrantly expressed sarcoidosis.

Language: Английский

Citations

0
Neural development goes retro: Gags as essential modulators of synapse formation DOI Creative Commons
Yung‐Heng Chang, Josh Dubnau

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(2), P. e3003032 - e3003032

Published: Feb. 19, 2025

Neurodevelopment requires dynamic control of synapse number. A new study in PLOS Biology reveals that the gag protein Copia, an active retrotransposon, forms virus-like capsids transfer its own RNA across Drosophila neuromuscular junction. Here, Copia acts antagonistically with Arc, another retrotransposon protein, to regulate formation.

Language: Английский

Citations

0
Nanopore-based DNA long-read sequencing analysis of the aged human brain DOI Creative Commons
Paulino Ramirez, Wenyan Sun, Shiva Kazempour Dehkordi

et al.

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

Published: Feb. 5, 2024

ABSTRACT Studies in laboratory models and postmortem human brain tissue from patients with Alzheimer’s disease have revealed disruption of basic cellular processes such as DNA repair epigenetic control drivers neurodegeneration. While genomic alterations regions the genome that are rich repetitive sequences, often termed “dark regions,” difficult to resolve using traditional sequencing approaches, long-read technologies offer promising new avenues explore previously inaccessible genome. In current study, we leverage nanopore-based whole-genome extracted frontal cortex at early late stages disease, well age-matched controls, analyze retrotransposon insertion events, non-allelic homologous recombination (NAHR), structural variants methylation within loci other repetitive/dark Interestingly, find events element-associated NAHR particularly enriched centromeric pericentromeric aged brain, ribosomal (rDNA) is subject a high degree compared We detect trending increase potential somatic retrotransposition small interfering nuclear element (SINE) AluY late-stage differential changes elements retrotransposons according stage. Taken together, our analysis provides first sequencing-based NAHR, variants, points toward transposable elements, centromeric/pericentromeric rDNA hotspots for variation.

Language: Английский

Citations

3
From the genome's perspective: Bearing somatic retrotransposition to leverage the regulatory potential of L1 RNAs DOI Creative Commons
Damiano Mangoni,

Anna P. Mazzetti,

Federico Ansaloni

et al.

BioEssays, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 9, 2024

Transposable elements (TEs) are mobile genomic constituting a big fraction of eukaryotic genomes. They ignite an evolutionary arms race with host genomes, which in turn evolve strategies to restrict their activity. Despite being tightly repressed, TEs display precisely regulated expression patterns during specific stages mammalian development, suggesting potential benefits for the host. Among TEs, long interspersed nuclear element (LINE-1 or L1) has been found be active neurons. This activity prompted extensive research into its possible role cognition. So far, no cause-effect relationship between L1 retrotransposition and brain functions conclusively identified. Nevertheless, accumulating evidence suggests that interactions RNAs RNA/DNA binding proteins encode messages cells utilize activate repress entire transcriptional programs. We summarize recent findings highlighting at non-coding level early embryonic development. propose hypothesis mutualistic mRNAs cell. In this scenario, tolerate certain rate leverage regulatory effects L1s as on potentiating mitotic potential. turn, benefit from cell's proliferative state increase chance mobilize.

Language: Английский

Citations

1
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

Citations

0
Transposable element small and long RNAs in aging brains and implications in Huntington's and Parkinson's disease DOI Open Access
Gargi Dayama, Shruti Gupta, Brianne K. Connizzo

et al.

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

Published: Oct. 25, 2024

ABSTRACT Transposable Elements (TEs) are implicated in aging and neurodegenerative disorders, but the impact of brain TE RNA dynamics on these phenomena is not fully understood. Therefore, we quantified changes post-mortem human mouse brains disorders Huntington’s Disease (HD) Parkinson’s (PD). We tracked small RNAs (smRNAs) expression landscape to assess relationship active processing from long (lnRNAs). Human transcriptomes BrainSpan Atlas displayed a significant shift smRNA patterns at age 20 years, whereas lacked any such marked change, despite clear aging-associated mRNA levels. frontal cortex pronounced sense smRNAs during with negative between lnRNAs indicative associated regulatory effects. Our analysis revealed dysregulation HD, while PD showed stronger lnRNAs, potentially correlating early average death for HD relative PD. Furthermore, TE-silencing factor TRIM28 was down-regulated only brains, possibly explaining lack substantial brains. study suggests may serve as novel biomarkers disorders.

Language: Английский

Citations

0
Human Endogenous Retroviruses and Their Putative Role in Pathogenesis of Alzheimer’s Disease, Inflammation, and Senescence DOI Creative Commons

Patrycja Kozubek,

Julia Kuźniar,

Magdalena Czaja

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 13(1), P. 59 - 59

Published: Dec. 30, 2024

The human endogenous retroviruses (HERVs) are ancient exogenous that were embedded in the germline over 30 million years ago and underwent an endogenization process. They make up roughly 8% of genome. HERVs exhibit many physiological non-physiological functions; for example, they play a role development diseases. have been shown to affect carcinogenesis by modifying expression host genes through their functions as enhancers promoters. Additionally, some molecules derived from may stimulate immune system. Recently research has focused on effect neurodegenerative diseases, including Alzheimer’s disease (AD), which is most common cause dementia. AD also linked significant deterioration quality life. article aims highlight potential diseases such senescence. Moreover, it estimated be targets diagnosis therapy AD.

Language: Английский

Citations

0