Mobile DNA最新文献

{"title":"Strict retroelement regulation is frequently lost following cancer transformation and generates a promising reservoir of cancer biomarkers.","authors":"Eric Russ, Sergey Iordanskiy","doi":"10.1186/s13100-025-00376-7","DOIUrl":"10.1186/s13100-025-00376-7","url":null,"abstract":"<p><strong>Background: </strong>Retroelements are repetitive sequences that comprise 42% of the human genome and are strictly regulated through various epigenetic mechanisms. Examining retroelement expression on a locus-specific level in relation to cancer can uncover distinct disease signatures.</p><p><strong>Results: </strong>Using over 5000 RNA-sequencing samples, we assessed retroelement transcription across 23 tissue systems, 159 cell types, 1019 cancer cell lines, and cells isolated from various stages of embryogenesis using the specialized software tool, Telescope. In healthy individuals, 11,388 retroelements were found to be actively transcribed and dynamically regulated in a tissue- and cell type-dependent manner. Using the adult human body as a reference, we observed that 94% of cancer cell lines displayed elevated transcription of at least one cancer-specific retroelement, providing a three-fold larger reservoir of cancer biomarkers (1182) than our comparable analysis of annotated protein-coding genes (338). The precise retroelements that were transcribed following tumorigenesis were influenced by the originating location, with cancers of the blood, lungs, and soft tissue displaying the highest origin-specific activation. Moreover, nearly half of the cancer-specific retroelement loci, mostly from the HERV-H family, were found to be expressed during early embryonic development.</p><p><strong>Conclusions: </strong>Our data demonstrate that elevated transcription of certain tissue-specific and embryonic retroelements can be considered as a hallmark of tumorigenesis.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"37"},"PeriodicalIF":3.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene and transposable element expression in response to stress in temperate and tropical populations of Drosophila.","authors":"Miriam Merenciano, Daniel S Oliveira, Judit Salces-Ortiz, Rita Rebollo, Bianca Manfré, Bianca Menezes, Gabriel Krasovec, Camille Simonet, Sonia Janillon, Nelly Burlet, Claudia M A Carareto, Cristina Vieira, Marie Fablet","doi":"10.1186/s13100-025-00372-x","DOIUrl":"10.1186/s13100-025-00372-x","url":null,"abstract":"<p><strong>Background: </strong>The study of stress response in natural populations is crucial for understanding species local adaptation and evolution. In Drosophila, significant genetic diversity across populations from different geographical origins has been observed, emphasizing the influence of local environments.</p><p><strong>Results: </strong>In this study, we explored the impact of starvation and cold stress on the phenotypic and transcriptomic response of two natural populations of D. melanogaster and D. simulans from temperate and tropical regions. Additionally, we investigated the behavior and influence of transposable elements (TEs) in these types of stress, combining RNA-seq and ChIP-seq experiments, with high-quality long-read genome assemblies of all the strains. Our findings in D. melanogaster revealed that the transcriptomic response to stress is similar across geographical origins, whereas in D. simulans there is more variability. Notably, neither starvation nor cold induced a general activation of TEs in D. melanogaster or D. simulans, at least in the tissue and strains analysed in this study. Finally, we found three polymorphic TEs producing TE-chimeric transcripts associated with changes in nearby gene expression levels after stress.</p><p><strong>Conclusions: </strong>Overall, this study highlights the complexity of stress-TE interactions and their potential impact on adaptation. Understanding these dynamics contributes to the broader knowledge of how genetic and environmental factors interact to modulate gene expression, shaping an organism's ability to adapt to varying conditions.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"35"},"PeriodicalIF":3.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative structural analysis of IS21 transposition complexes using Cryo-EM and AlphaFold3.","authors":"Mercedes Spínola-Amilibia, Irene Rizzuto, Ernesto Arias-Palomo","doi":"10.1186/s13100-025-00374-9","DOIUrl":"10.1186/s13100-025-00374-9","url":null,"abstract":"<p><p>Transposition is a fundamental driver of genome evolution, enabling the movement of discrete DNA segments (transposons) within genomes. This process can modulate gene expression and contributes to the spread of antibiotic resistance and virulence factors. We recently determined different cryo-electron microscopy (cryo-EM) structures of the IS21 transposon, a widespread mobile genetic element that encodes IstA, a transposase, and IstB, a AAA + ATPase essential for DNA transposition. The reconstructions of these factors in the pre- and post-transposition states revealed key insights into the architecture and conformational dynamics of the transpososome. In parallel, we evaluated one of the newest structure prediction engines, AlphaFold3 (AF3), to help guide the structural work and explore its capacity to model these intricate protein-DNA assemblies. Here we present a focused comparison between the cryo-electron-microscopy structures of the IS21 transpososome and models generated with the public AF3 server. Overall, our findings show that while AF3 excels at predicting individual monomeric domains and select oligomeric arrangements, it struggles to capture some complex assemblies, conformational changes, and higher-order interactions critical for transposon function.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"34"},"PeriodicalIF":3.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type I interferons increase expression of endogenous retrovirus K102 and envelope protein in myeloid cells from patients with autoimmune disease.","authors":"Ethan Le, Fatemeh Moadab, Xiaoxing Wang, Rayan Najjar, Alison Bays, Kathryn M Hastie, Jeremy Shek, Erica Ollmann Saphire, Tomas Mustelin","doi":"10.1186/s13100-025-00371-y","DOIUrl":"10.1186/s13100-025-00371-y","url":null,"abstract":"<p><strong>Background: </strong>Autoantibodies against envelope (Env) protein encoded by human endogenous retrovirus group K (HERV-K) are prevalent in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but it remains unclear which proviruses are responsible for this autoantigen. It also remains poorly understood how the transcription of HERV-K loci is regulated in cells that can produce Env.</p><p><strong>Results: </strong>We aligned our neutrophil RNA sequencing data to the new telomere-to-telomere reference genome and found uniquely mapping transcripts from HERV-K101, K102, K104, K108, K109, K117 and ERVK5, of which only K102, K108, and K109 encode an intact Env. Expression of K102 and K108 were higher in SLE than in healthy donors or RA (p_adj < 0.05). Transcripts from these proviruses increased in response to interferon-α in monocytes and neutrophils from RA patients and healthy donors, but not in SLE, presumably because they have chronically elevated type I interferons in vivo. Indeed, HERV-K expression was significantly higher in SLE patients with high type I interferon gene signature. Tumor necrosis factor-α and other cytokines and TLR ligands also induced HERV-K102 and K108 transcripts. Interferon-α also increased detectable Env protein in monocytes, macrophages, and neutrophils from RA patients. Among the genes for epigenetic silencers of HERV-K, only TRIM28 was significantly decreased in SLE patients with high interferons (p_adj = 0.00024).</p><p><strong>Conclusions: </strong>Our data establish a role for interferons in maintaining increased HERV-K expression in SLE and suggest that interferons or other cytokines can upregulate HERV-K to similar levels in RA. A transient increase may also accompany normal immune responses, suggesting that endogenous retroviruses may have been co-opted for efficient immune responses.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"36"},"PeriodicalIF":3.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transposable element dynamics in glioblastoma stem cells: insights from locus-specific quantification.","authors":"Mattia D Pizzagalli, Yusuke Suita, Owen P Leary, Nikos Tapinos","doi":"10.1186/s13100-025-00370-z","DOIUrl":"10.1186/s13100-025-00370-z","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma, the most common primary malignant brain tumor, has a median survival of less than two years. This is due in part to a subpopulation of cells called glioblastoma stem cells (GSCs), which drive tumor recurrence. Transposable elements (TEs) are expressed at higher levels in cancer stem cells, enhancing the oncogenic potential and plasticity of cells through changes in gene expression, fusion transcript generation, and genomic rearrangement.</p><p><strong>Results: </strong>Leveraging a large previously published dataset, we investigated the expression of TEs in bulk RNA sequencing data from 42 GSCs to identify subpopulations defined by their TE expression profile. Using telescope, a locus-specific approach to quantifying TE expression, we identified 858 TE loci that were expressed and defined two groups of GSCs using a consensus clustering approach. These TE-driven clusters displayed significant differences in both transcription factor (TF) and gene expression, with one group significantly enriched for a mesenchymal signature based on Gene Set Enrichment Analysis. Next, we extracted the locations and sequences of the TE regulatory domains and elucidated TF binding motifs within the TE sequences. This showed that the SOX11 consensus motif was enriched in the 5' untranslated region of differentially expressed long interspersed nuclear elements (LINE). SOX11, a known inducer of LINE expression, was significantly under-expressed in the mesenchymal GSC cluster, which correlated with the concurrent decreased expression of LINE transcripts. These loci also overlapped with the enhancer elements of genes that were significantly downregulated, suggesting a potential link between TF binding to TE regulatory regions and gene expression.</p><p><strong>Conclusions: </strong>Although further mechanistic studies are required, the identified link between TE location, TE and TF expression, and corresponding gene expression suggests that TEs may play a regulatory role in GSC transcription regulation. The current findings highlight the need for further investigation into the role of TEs in defining the gene regulatory and expression landscapes of GSCs. Future studies in this area could have therapeutic implications, given that glioblastoma recurrence may be driven by these cells.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"33"},"PeriodicalIF":3.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Escherichia coli proteins uL29 and ACP stabilize the Tn7-encoded TnsD and its DNA binding.","authors":"Shani B Leyva Camacho, Lindsay A Matthews, Alba Guarné","doi":"10.1186/s13100-025-00369-6","DOIUrl":"10.1186/s13100-025-00369-6","url":null,"abstract":"<p><p>Tn7 mobile genetic elements are known for their sophisticated target-site selection mechanisms and, in some cases, programmability. Recognition of target sites is mediated by designated transposon-encoded proteins and modulated by host factor proteins. In the case of the CRISPR-associated Tn7 elements from the type V-K, the ribosomal protein uS15 is an integral component of recruitment complex that promotes R-loop completion. Previous biochemical work also revealed that the ribosomal protein uL29 and the acyl carrier protein (ACP) influence Tn7 transposition frequency in vitro. However, how uL29 and ACP regulate the formation of the Tn7 targeting complex remains unclear. The prototypical Tn7 element encodes a heteromeric transposase (TnsA, TnsB), a AAA + adaptor (TnsC), and two target-site selection proteins (TnsD and TnsE). TnsD targets a highly conserved site at the end of the glmS gene (attTn7). However, poor protein stability has precluded the molecular characterization of how TnsD recognizes its target site. Here, we show that ACP and uL29 interact with the C-terminal region of TnsD through reciprocal electrostatic interactions, in turn, mitigating its tendency to aggregate. Additionally, we identify the uL29 and ACP residues that mediate the interaction with TnsD and stimulate DNA binding. These results unveil unique features of the TnsD-mediated target-site selection complex.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"32"},"PeriodicalIF":3.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A plan or pandemonium? The conundrum of retrotransposon activation in cancer.","authors":"Elina Zueva","doi":"10.1186/s13100-025-00368-7","DOIUrl":"10.1186/s13100-025-00368-7","url":null,"abstract":"","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"31"},"PeriodicalIF":3.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-depth analysis of endogenous retrovirus expression in glioblastoma.","authors":"Daniel A Murimi-Worstell, Irene B Murimi-Worstell, Farrah M Roy, Aidan Burn, Michael Freeman, Ralph B Puchalski, John M Coffin","doi":"10.1186/s13100-025-00365-w","DOIUrl":"10.1186/s13100-025-00365-w","url":null,"abstract":"<p><strong>Background: </strong>Human endogenous retroviruses (HERVs) are remnants of ancient viral infections and comprise 6-8% of the human genome. Their biological functions in cancer remain poorly understood, especially in glioblastoma, the most common and deadly primary brain cancer in adults. Prior studies on HERV expression in glioblastoma have yielded conflicting results. Here, we employed orthogonal computational pipelines to address these limitations.</p><p><strong>Results: </strong>Locus-specific analysis revealed marked heterogeneity of transcription among HERVs within the same clade. We found that individual HERV proviruses are more than twice as likely to be underexpressed in glioblastoma than overexpressed and that most differentially expressed HERVs are exonized within transcripts. These HERVs are enriched in the 3'-terminal exons of transcripts, associated with alternative polyadenylation and contribute conserved polyadenylation signals. We identified HERV expression patterns associated with glioblastoma subtypes and anatomic features. We also identified three proviruses or proviral fragments of particular interest including one associated with survival and one exonized within a currently unannotated cancer-specific transcript. Among the most recently integrated clade of HERVs, excluding solo-LTRs, only the HML-2 provirus at 1q22 is overexpressed in glioblastoma. We report previously undescribed transcripts incorporating this provirus that may encode several proteins.</p><p><strong>Conclusions: </strong>This study represents the first systematic exploration of the heterogeneity of HERV expression between anatomic features of any cancer. It shows that exaptation of HERV polyadenylation signals and HERV-associated APA are widespread in the human transcriptome and identifies critical structural information regarding the HML-2 1q22 provirus transcript, which has been the focus of several recent analyses. Our findings underscore the importance of locus-specific and anatomic feature-specific HERV analysis and suggest structural and functional roles for HERVs in glioblastoma-associated transcripts.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"29"},"PeriodicalIF":4.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Locus-specific HERV expression associated with hepatocellular carcinoma.","authors":"Hui Wen, Marcos Pérez-Losada, Lopa Mishra, Keith A Crandall","doi":"10.1186/s13100-025-00367-8","DOIUrl":"10.1186/s13100-025-00367-8","url":null,"abstract":"<p><strong>Background: </strong>Human endogenous retroviruses (HERVs) harbor accessory proteins that influence cellular processes and have been linked to a wide variety of diseases, including cancer. This study investigates locus-specific HERV expression and its association with gene dysregulation in hepatocellular carcinoma (HCC), a highly prevalent and deadly form of liver cancer worldwide.</p><p><strong>Methods: </strong>We analyzed RNASeq data from 424 HCC samples from The Cancer Genome Atlas (TCGA), which comprised 371 tumor and 50 matched normal tissues from a total of 371 hepatocellular carcinoma participants. We employed Telescope to identify and quantify HERV expression across the total RNA sequencing data.</p><p><strong>Results: </strong>The majority of differentially expressed HERVs exhibited reduced expression in tumor tissue (166 downregulated vs. 50 upregulated), suggesting a potential functional role of HERV expression patterns in shaping the pathophysiological landscape of HCC. Specifically, the suppression of HERV-H family members, which are known to regulate cellular differentiation, may contribute to tumor dedifferentiation, increased plasticity, and enhanced metastatic potential. This loss of differentiation control and increased adaptability may play a critical role in driving the progression of liver cancer.</p><p><strong>Discussion: </strong>Our study highlights a significant association of HERV expression with HCC, highlighting the differential regulation of specific HERV families in tumor tissue. For example, HERVH and ERVLE families showed consistent downregulation in tumor samples, while HERVE and HERV9 were more commonly upregulated. These shifts may reflect underlying changes in transcriptional regulation or chromatin structure between normal and malignant tissues. Rather than indicating a singular functional role, the observed expression patterns likely reflect a multifaceted relationship between HERVs and tumor biology. Further studies will be needed to determine whether these expression differences contribute to, or result from, tumor progression and to explore their potential as biomarkers or therapeutic targets.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"30"},"PeriodicalIF":4.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring transposable elements: new horizons in cancer diagnostics and therapeutics.","authors":"Ahlam Chaaban, Reem Sleem, Jana Santina, Mohamad Rima, José-Noel Ibrahim","doi":"10.1186/s13100-025-00366-9","DOIUrl":"10.1186/s13100-025-00366-9","url":null,"abstract":"<p><p>Transposable elements (TE), also called transposons, are repetitive DNA sequences making up half of the human genome. Initially, TEs were described as \"junk DNA\" because they lack specific function. However, they have been recognized for their ability to replicate and integrate into different genomic locations; this \"jumping gene\" activity results in genomic instability, variation of the chromosomal architecture, and transcriptional dysregulation, all of which represent major hallmarks of cancer. In this respect, the involvement of TE in tumorigenesis was extensively studied and their role as diagnostic and therapeutic tools in cancer is now well-established. Transposons' products, including TE-derived cancer antigens, transcripts, and associated epigenetic modifications, mainly hypomethylation, were found to be promising biomarkers in several types of cancer ensuring early disease detection and prognosis. In addition, TE are currently used to design innovative approaches, with transposon-based systems, namely, Sleeping Beauty and PiggyBac, enabling precise genomic modifications and novel strategies for cancer therapy. Therefore, the aim of this review is to provide an overview on the dual application of TE as diagnostic and therapeutic tools in cancer, paving the way to improved clinical outcomes. CLINICAL TRIAL NUMBER: Not applicable.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"28"},"PeriodicalIF":3.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}