Transposon–host arms race: a saga of genome evolution

Trends in Genetics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity

Journal of General Virology, Год журнала: 2025, Номер 106(1)

Опубликована: Янв. 13, 2025

Human immunodeficiency virus (HIV) is an exemplar virus, still the most studied and best understood a model for mechanisms of viral replication, immune evasion pathogenesis. In this review, we consider earliest stages HIV infection from transport virion contents through cytoplasm to integration genome into host chromatin. We present holistic virus-host interaction during pivotal stage infection. Central process capsid. The last 10 years have seen transformation in way understand capsid structure function. review key discoveries our latest thoughts on as dynamic regulator innate chromatin targeting. also accessory proteins Vpr Vpx because they are incorporated particles where collaborate with capsids manipulate defensive cellular responses argue that effective regulation uncoating immunity define pandemic potential pathogenesis, how comparison different lineages can reveal what makes lentiviruses special.

Язык: Английский

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Multi-ancestry GWAS reveals loci linked to human variation in LINE-1- and Alu-insertion numbers

Translational Medicine of Aging, Год журнала: 2025, Номер 9, С. 25 - 40

Опубликована: Янв. 1, 2025

Язык: Английский

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Interplay between Two Paralogous Human Silencing Hub (HuSH) Complexes in Regulating LINE-1 Element Silencing

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 3, 2024

The Human Silencing Hub (HuSH) complex silences retrotransposable elements in vertebrates. Here, we identify a second HuSH complex, designated HuSH2, which is centered around TASOR2, paralog of the core TASOR protein HuSH. Our findings reveal that and HuSH2 localize to distinct non-overlapping genomic loci. Specifically, localizes represses LINE-1 retrotransposons, whereas targets KRAB-ZNFs interferon signaling response genes. We use silico structure predictions simulate MPP8 interactions with paralogs, guiding amino acid substitutions disrupted binding complexes. These transgenes other constructs importance quantities regulating activity. Furthermore, our results suggest dynamic changes TASOR2 expression enable cells finely tune HuSH-mediated silencing. This study offers insights into interplay complexes, highlighting their vital role retrotransposon regulation. identifies paralogous HuSH, its localization function. while regulates

Язык: Английский

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Two HUSH complexes connect a direct LINE to innate immunity

Molecular Cell, Год журнала: 2024, Номер 84(15), С. 2801 - 2803

Опубликована: Авг. 1, 2024

Язык: Английский

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Multi-ancestry GWAS reveals loci linked to human variation in LINE-1- and Alu-copy numbers

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 11, 2024

Long INterspersed Element-1 (LINE-1; L1) and Alu are two families of transposable elements (TEs) occupying ∼17% ∼11% the human genome, respectively. Though only a small fraction L1 copies is able to produce machinery mobilize autonomously, degenerate can hijack their functional

Язык: Английский

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TASOR expression in naive embryonic stem cells safeguards their developmental potential

Cell Reports, Год журнала: 2024, Номер 43(11), С. 114887 - 114887

Опубликована: Окт. 24, 2024

Язык: Английский

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Transposable element small and long RNAs in aging brains and implications in Huntington's and Parkinson's disease

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 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.

Язык: Английский

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The HUSH epigenetic repressor complex silences PML nuclear body-associated HSV-1 quiescent genomes

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(49)

Опубликована: Ноя. 26, 2024

Herpes simplex virus 1 (HSV-1) latently infected neurons display diverse patterns in the distribution of viral genomes within nucleus. A key pattern involves quiescent HSV-1 sequestered promyelocytic leukemia nuclear bodies (PML NBs) forming DNA-containing PML-NBs (vDCP NBs). Using a cellular model that replicates vDCP NB formation, we previously demonstrated these are chromatinized with H3.3 histone variant modified on its lysine 9 by trimethylation (H3.3K9me3), mark associated transcriptional repression. Here, identify HUSH complex and effectors, SETDB1 MORC2, as crucial for acquisition H3K9me3 PML NB-associated maintenance ChIP-seq analyses show association entire genome. Inactivating HUSH–SETDB1–MORC2 before infection significantly reduces genome, minimal impact aside from expected changes LINE-1 retroelements. Depletion HUSH, SETDB1, or MORC2 alleviates repression primary human fibroblasts induced pluripotent stem cell–derived sensory (hiPSDN). We found protein ICP0 induces degradation via proteasome machinery. This process is concurrent depletion capability to reactivate silenced hiPSDN. Overall, our findings underscore robust antiviral function repressor against herpesvirus modulating chromatin marks linked repression, thus presenting promising avenues anti-herpesvirus therapeutic strategies.

Язык: Английский

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RNA binding by Periphilin plays an essential role in initiating silencing by the HUSH complex

Nucleic Acids Research, Год журнала: 2024, Номер unknown

Опубликована: Дек. 11, 2024

The human silencing hub (HUSH) complex is a transcription-dependent, epigenetic repressor that provides genome-wide immunosurveillance system for the recognition and of newly-integrated retroelements. core HUSH TASOR, MPP8 Periphilin, represses these retroelements through SETDB1-mediated H3K9me3 deposition MORC2-dependent chromatin compaction. HUSH-dependent RNA-mediated, yet no component contains recognised RNA-binding domain. Here we used an unbiased approach to identify which was able bind RNA determine whether essential function. We Periphilin as major show Periphilin's N-terminal domain both binding independent its interaction with TASOR or MPP8, sufficient targeting. artificial tethering HUSH-insensitive, nascent transcript, enabled transcript. This allowed region be removed such only C-terminal required oligomerisation TASOR. therefore predominant protein this activity.

Язык: Английский

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