Mobile DNA最新文献

How endogenous retroviral elements (ERVs), a family of transposable elements, may promote tumor progression is not well understood. Tripartite motif-containing 28 (TRIM28/TIF1b/KAP1) is a key transcriptional co-repressor protein that represses ERV expression in many cell types including embryonic stem cells, neural progenitor cells, differentiated adult cells, and cancer cells. In this study, we investigated the effect of Trim28 deletion on the expression of ERVs using an immune competent genetically engineered mouse model for prostate cancer. We found Trim28 deletion in prostate tumors led to the expression of ERVs in prostates from both hormonally intact and castrated mice. ERVs can regulate the expression of neighboring genes, and we detected increased expression of several protein-coding genes near overexpressed ERVs. Our data suggest that Trim28 deletion in prostate tumor epithelial cells may promote an innate immune response. However, Trim28 deletion also led to excessive deposition of tumor extracellular matrix (ECM). Our findings suggest that ECM alterations downstream of ERV derepression could affect immune cells in the tumor microenvironment and may promote tumor progression.

Background: Transposable elements (TEs) are widespread mobile DNA sequences that shape genome structure, function, and evolution. Although automated tools exist for the de novo identification and classification of TEs, their output often requires manual refinement to generate accurate consensus sequences for individual TE families. This curation process is essential but remains time-consuming and inaccessible to many researchers, particularly those without bioinformatics expertise or access to sufficient computing resources. To address this gap, we developed ColabCuraTE, a web-based, user-friendly pipeline implemented in Google Colaboratory that enables manual curation of TEs without the need for local software installation or advanced programming skills.

Results: ColabCuraTE includes built-in visualization tools and guides users through a streamlined workflow-from TE copy identification, alignment extension, and refinement, to consensus sequence generation and TE family analysis. We validated the pipeline using both megabase-sized and gigabase-sized genomes and found that it reliably improves the quality and completeness of TE consensus sequences compared to outputs from automated de novo TE annotation tools.

Conclusions: ColabCuraTE enables easier participation in TE curation by removing infrastructure and expertise requirements that typically limit participation in genomic research. It excels at the targeted curation of individual TE families but can also be used for large-scale curation efforts when deployed via a course or workshop. Its accessibility, intuitive interface, and compatibility with existing tools make it a valuable resource for both researchers and educators. ColabCuraTE enables broader participation in TE annotation efforts and supports the integration of undergraduates in genomics research.

Background: Long Interspersed Nuclear Elements-1 (LINE-1, L1) are transposable elements that make up roughly 17% of the human genome. These elements can copy and insert themselves into new genomic locations (Kazazian and Moran, N Engl J Med 377:361-370, 2017). Typically, LINE-1 is repressed in healthy tissues but may become activated in various human diseases. LINE-1 expression has been associated with aging (Simon, et al., Cell Metab 29:871-885.e5, 2019; De Cecco et al. Nature 566:73-78, 2019; Della Valle et al. Nat Rev Genet 26:1-12, 2025), neurodegenerative disorders (Roy et al., Acta Neuropathol 148:75, 2024;Frost and Dubnau, Annu Rev Neurosci 47:123-143, 2024; Ravel-Godreuil et al. FEBS Lett 595:2733-2755, 2021), cancer (Rodriguez-Martin et al., Nat Genet 52:306-319, 2020; Taylor et al. Cancer Discov 13:2532-2547, 2023; Solovyov et al. Nat Commun 16:2049, 2025), and autoimmune diseases (Rice et al., N Engl J Med 379:2275-2277, 2018), (Carter et al., Arthritis Rheumatol 72:89-99, 2020). Despite the strong association between LINE-1 expression and disease, the regulatory mechanisms controlling the expression of LINE-1-encoded ORF1p and ORF2p and the link between LINE-1 activity and cancer cell survival remain poorly understood. Gaining insights into these regulatory pathways may help elucidate how LINE-1 contributes to disease pathogenesis.

Results: To identify upstream regulators of LINE-1 and genes associated with LINE-1 activity-dependent lethality, we developed a dual-reporter system that simultaneously monitors the protein levels of LINE-1-encoded ORF1p and ORF2p (wild-type or catalytically inactive EN/RT mutant). Using genome-wide CRISPR/Cas9-based screens with this system, we identified candidate genes that may influence LINE-1 regulation at multiple levels, including RNA and protein expression. Alongside known factors such as the HUSH complex, the screens revealed additional genes not previously linked to LINE-1 regulation, suggesting possible new regulatory mechanisms for ORF1p and ORF2p expression. We also identified genes whose loss correlated with reduced viability in a manner dependent on LINE-1 activity. These findings collectively provide a broad resource for exploring cellular factors that may modulate LINE-1 expression and activity.

Conclusion: This study provides a resource for investigating the cellular regulation of LINE-1, highlighting distinct candidate factors that may modulate ORF1p and ORF2p expression and influence LINE-1 activity-associated cytotoxicity. While functional validation of these candidate regulators remains necessary, the findings offer a foundation for future studies aimed at experimentally confirming their roles and elucidating the molecular mechanisms underlying LINE-1 regulation and its potential contributions to disease contexts.

Transposable elements (TEs) occupy a significant fraction of a wide variety of eukaryotic genomes and can be domesticated into functional sequences harbouring a coding or regulatory potential. While studies in mammals have revealed that retrotransposons can frequently give rise to tissue-specific transcriptional enhancers our understanding of this phenomenon in other vertebrate groups is scarcer. Here, we examined TE occupancy at tissue-specific nucleosome free regions (NFRs) which are not annotated as promoters in the amphibian model organism Xenopus tropicalis. We report three distinct miniature inverted-repeat TEs (MITEs) enriched at distal liver-specific NFRs and belonging to the hAT, Harbinger and Kolobok superfamilies of DNA transposons. These MITEs show a marked depletion at NFRs specific to the bone tissue, probably reflecting a process of negative selection. In addition, we show that they are enriched for transcription factor binding sites known to be bound by key regulators of liver biology, hematopoiesis, and the immune system, and that they are more likely to be located in the vicinity of genes specifically expressed in the liver than other MITE copies that are not associated to a NFR. We also find that these MITEs are not present at orthologous positions in the genome of the related allotetraploid frog Xenopus laevis, while they globally are abundant in this species. We discuss how independent bursts of MITE amplification followed by subsequent domestication episodes might independently have given rise to liver-specific transcriptional enhancers in the Xenopus tropicalis lineage.

Nearly half of the human genome consists of transposable elements, among which endogenous retroviruses, remnants of ancient retroviral infections, represent some of the most evolutionarily intriguing due to their paradoxical functional duality. While research has documented functional ERV exaptation in key biological processes, these elements have also been associated with age-related diseases, particularly cancer. This apparent contradiction presents an evolutionary question: why would potentially disruptive elements persist in genomes over evolutionary time? Here we review the complex relationship between ERVs, aging and cancer to address this question. After reviewing the physiological roles of ERVs, we explore how the transcriptional activation of normally repressed ERVs may function as an evolutionary-conserved genomic surveillance system that, when triggered by cellular stressors, generates viral-like nucleic acids and proteins that activate pathways to potentially eliminate cancerous cells. Conversely, we discuss how cancer cells could appropriate ERV expression to distort cellular processes, promoting inflammation and senescence that ultimately facilitate tumor progression. Despite this duality, we advance a novel hypothesis that many ERVs have been exapted in mammalian genomes primarily as defense mechanisms against tumorigenesis. This evolutionary perspective provides a framework for understanding both the persistence of ERVs in our and other mammals' genomes and their intriguing roles in cancer biology. Moreover, even after tumor development, ERVs can be exploited by immunotherapy due to their canonical function as regulators of the immune response, positioning them as emerging central elements in cancer treatment strategies. This work offers new insights into these endogenous retroviruses' evolutionary significance and potential applications in cancer therapeutics and diagnostics.

Background: The recognition that transposable elements (TEs) play important roles in many biological processes has elicited growing interest in analyzing sequencing data derived from this 'dark genome'. This goal is complicated by the highly repetitive nature of these sequences in genomes, requiring the deployment of several problem-specific tools as well as the curation of appropriate genome annotations. This pipeline aims to make the analysis of TE sequences and their expression more generally accessible.

Results: The TE-Seq pipeline conducts an end-to-end analysis of RNA sequencing data, examining both genes and TEs, and is compatible with most eukaryotic species. It implements computational methods tailor-made for TEs, and produces a comprehensive analysis of TE expression at both the level of the individual element and at the TE clade level. Furthermore, if supplied with long-read DNA sequencing data, it is able to assess TE expression from non-reference (polymorphic) loci. As a demonstration, we analyzed proliferating, early senescent, and late senescent human lung fibroblast RNA-Seq data, and created a custom reference genome and annotations for this cell strain using Nanopore sequencing data. We found that several retrotransposable element clades were upregulated in senescence, which included non-reference, intact, and potentially active elements.

Conclusions: TE-Seq is made available as a Snakemake pipeline which can be obtained at https://github.com/maxfieldk/TE-Seq .

Transposable elements (TEs) are dynamic components of eukaryotic genomes, playing a crucial role in genome evolution and plasticity, particularly in unstable regions such as chromosome ends. In the globally significant fungal pathogen Fusarium oxysporum, we identified and characterized a novel family of non-LTR retrotransposons named FoTeRs (F. oxysporum Telomeric Retrotransposons). These elements are consistently and uniquely localized at chromosome ends, representing a rare example of site-specific TE integration. Phylogenetic analysis confirmed that FoTeRs form a distinct clade with other telomere-targeting retrotransposons, suggesting a shared evolutionary history and a convergent mechanism for telomeric integration. We found that individual FoTeR elements exhibit a duality in their evolutionary status. Putatively functional elements are under strong purifying selection, indicating that their protein-coding regions are highly conserved. This contrasts with the presence of other, non-functional copies that exhibit signs of mutational decay, a process accelerated by Repeat-Induced Point (RIP) mutations -a fungal-specific defense mechanism. The high density of upstream variable number tandem repeats (VNTRs) also contributes to their genomic plasticity. Furthermore, FoTeRs frequently co-localize with host Telomere-Linked Helicases (TLHs), suggesting a potential functional link in telomere maintenance. This study provides crucial insights into the role of TEs in shaping the genome architecture and adaptive potential of this important fungal pathogen.