Mobile DNA最新文献

{"title":"Retand LTR-retrotransposons in plants: a long way from pol to 3'LTR.","authors":"Carlos M Vicient","doi":"10.1186/s13100-025-00354-z","DOIUrl":"10.1186/s13100-025-00354-z","url":null,"abstract":"<p><strong>Background: </strong>Plant Gypsy LTR-retrotransposons are classified into lineages according to the phylogenetic relationships of the reverse transcriptase. Retand is a lineage of non-chromovirus elements characterized by the presence of a long internal region compared to other lineages.</p><p><strong>Results: </strong>This work focuses on the identification and characterization of Potentially Recently Active Retand Elements (PRAREs) in 617 genomic sequence assemblies of Viridiplantae species. The Retand elements were considered PRAREs if their LTRs and insertion sequences were identical, and the sizes of their internal regions and LTRs did not differ by more than 2% from the consensus. A total of 2,735 PRAREs were identified, distributed in 122 clusters corresponding to 34 species, with copy numbers per cluster varying between 1 and 180. They are present in Eudicotyledons and Liliopsida but not in other groups of plants. Some PRAREs are non-autonomous elements, lacking some of the typical LTR retrotransposon coding domains. The size of the POL-3'LTR regions varies between 2,933 and 6,566 bp, and in all cases, includes potential coding regions oriented antisense to the gag and pol genes. 97% of the clusters contain antisense ORFs encoding the TRP28 protein domain of unknown function. The analysis of the consensus TRP28 domain indicates that it probably can bind DNA. About half of the PRAREs contain arrays of tandem repeats in the POL-3'LTR region.</p><p><strong>Conclusions: </strong>The large internal region of the Retand elements is due to the presence of a long POL-3'LTR region. This region frequently contains arrays of tandem repeats that contribute to the expansion of this area. The presence of antisense ORFs in the POL-3'LTR region is also a common feature in these elements, many of which encode proteins with conserved domains, especially the TRP28 domain. The possible function of these TRP28-containing proteins is unknown, but their potential DNA binding capacity and the comparison with similar genes in some retroviruses suggest that they may play a regulatory role in the Retand transposition process.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"15"},"PeriodicalIF":4.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772883","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":"Subtelomeric repeat expansion in Hydractinia symbiolongicarpus chromosomes.","authors":"Tetsuo Kon, Koto Kon-Nanjo, Oleg Simakov","doi":"10.1186/s13100-025-00355-y","DOIUrl":"10.1186/s13100-025-00355-y","url":null,"abstract":"<p><p>Despite the striking conservation of animal chromosomes, their repetitive element complements are vastly diverse. Only recently, high quality chromosome-level genome assemblies enabled identification of repeat compositions along a broad range of animal chromosomes. Here, utilizing the chromosome-level genome assembly of Hydractinia symbiolongicarpus, a colonial hydrozoan cnidarian, we describe an accumulation of a single 372 bp repeat unit in the subtelomeric regions. Based on the sequence divergence, its partial affinity with the Helitron group can be detected. This sequence is associated with a repeated minisatellite unit of about 150 bp. Together, they account for 26.1% of the genome (126 Mb of the 483 Mb). This could explain the genome size increase observed in H. symbiolongicarpus compared with other cnidarians, yet distinguishes this expansion from other large cnidarian genomes, such as Hydra vulgaris, where such localized propagation is absent. Additionally, we identify a derivative of an IS3EU-like DNA element accumulated at the putative centromeric regions. Our analysis further reveals that Helitrons generally comprise a large proportion of H. symbiolongicarpus (11.8%). We investigated Helitron presence and distributions across several cnidarian genomes. We find that in Nematostella vectensis, an anthozoan cnidarian, Helitron-like sequences were similarly accumulated at the subtelomeric regions. All these findings suggest that Helitron derivatives are prone to forming chromosomal extensions in cnidarians through local amplification in subtelomeric regions, driving variable genome expansions within the clade.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"14"},"PeriodicalIF":4.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710754","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":"IS26 carrying bla_KPC-2 mediates carbapenem resistance heterogeneity in extensively drug-resistant Klebsiella pneumoniae isolated from clinical sites.","authors":"Zhiyun Guo, Xia Qin, Maokui Yue, Lingling Wu, Ning Li, Jing Su, Meijie Jiang","doi":"10.1186/s13100-025-00351-2","DOIUrl":"10.1186/s13100-025-00351-2","url":null,"abstract":"<p><strong>Background: </strong>Due to the widespread and irrational use of antibiotics, the emergence and prevalence of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) have become a major challenge in controlling bacterial infections in hospitals. The bla_KPC-2 gene located on mobile genetic elements has further complicated the control of resistant bacteria transmission.</p><p><strong>Results: </strong>In this study, K. pneumoniae strains were isolated from blood cultures of patients. Using the Kirby-Bauer disk diffusion method, we found carbapenem resistance heterogeneity. The resistant subpopulation KPTA-R1 and the sensitive subpopulation KPTA-S1 were purified. Whole-genome sequencing revealed that the bla_KPC-2 gene in KPTA-R1 was located on an IncFII plasmid (pKPC-R), within a composite transposon (PCTs) formed by two direct repeats of IS26 elements. The structure was identified as IS26-RecA-ISKpn27-bla_KPC-2-ISKpn6-IS26. However, in KPTA-S1, a similar plasmid, pAR-S, lacked this segment. Sequence comparison analysis indicates that the deletion of this bla_KPC-2 encoding sequence in this IncFII plasmid is associated with transposition activity mediated by IS26. Multi-sequence comparison of the plasmids showed that the IS26 transposon facilitated the sequence polymorphism of these plasmids.</p><p><strong>Conclusion: </strong>This study reveals the key role of IS26-mediated transposition activity, through homologous recombination, in the emergence of carbapenem resistance heterogeneity in clinical K. pneumoniae strains carrying bla_KPC-2. IS26 is able to promote the evolution of resistance in the IncFII plasmid, and through copy-in cointegration or targeted conservative cointegration may result in the acquisition or loss of antibiotic resistance, which may affect clinical care and pose a public health risk.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"13"},"PeriodicalIF":4.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701083","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":"Association of a 7.9 kb Endogenous Retrovirus Insertion in Intron 1 of CD36 with Obesity and Fat Measurements in Sheep.","authors":"Ahmed A Saleh, Ali Shoaib Moawad, Naisu Yang, Yao Zheng, Cai Chen, Xiaoyan Wang, Bo Gao, Chengyi Song","doi":"10.1186/s13100-025-00349-w","DOIUrl":"10.1186/s13100-025-00349-w","url":null,"abstract":"<p><strong>Background: </strong>Endogenous retroviruses (ERVs) enhance genetic diversity in vertebrates, including sheep. This study investigates the role of Ov-ERV-R13-CD36 within CD36 gene and its association with phenotypic traits in sheep. Analyzing 58 sheep genomes revealed that ERVs constitute approximately 6.02% to 10.05% of the genomic content. We identified 31 retroviral insertion polymorphisms (RIPs) from 28 ERV groups. Among these, Ov-ERV-R13-CD36, which is specifically classified as a beta retrovirus, was selected for further analysis due to its location in CD36 gene, known for its role in fat metabolism, obesity (OB), body weight (BW), and body condition score (BCS). We assessed the association of Ov-ERV-R13-CD36 with OB and BCS across six sheep breeds, utilizing data from 1,355 individuals.</p><p><strong>Results: </strong>Genomic analyses confirmed that Ov-ERV-R13-CD36 is located within CD36 gene on Chromosome 4, with polymorphisms across various sheep genomes. In a subset of 43 genomes, 22 contained the Ov-ERV-R13-CD36 insertion, while 21 exhibited wild-type variants. The studied animals showed variability in BCS and fat content associated with the Ov-ERV-R13-CD36 variant. Notably, Rahmani sheep exhibited a significantly higher BCS (4.62), categorized as obese, while Barki sheep displayed the lowest BCS (2.73), classified as thin to average. The association analysis indicated that sheep with the RIP^-/- genotype correlated with higher OB and BCS, particularly in Rahmani and Romanov x Rahmani breeds.</p><p><strong>Conclusions: </strong>Findings suggest that Ov-ERV-R13-CD36 within CD36 gene correlates with beneficial economic traits associated with OB and BCS, particularly in Rahmani and Romanov x Rahmani breeds. This indicates that Ov-ERV-R13-CD36 could be a valuable genetic marker for breeding programs aimed at enhancing traits like fat deposition and body condition in sheep.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"12"},"PeriodicalIF":4.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634139","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":"Further varieties of ancient endogenous retrovirus in human DNA.","authors":"Martin C Frith","doi":"10.1186/s13100-025-00348-x","DOIUrl":"10.1186/s13100-025-00348-x","url":null,"abstract":"<p><p>A retrovirus inserts its genome into the DNA of a cell, occasionally a germ-line cell that gives rise to descendants of the host organism: it is then called an endogenous retrovirus (ERV). The human genome contains relics from many kinds of ancient ERV. Some relics contributed new genes and regulatory elements. This study finds further kinds of ancient ERV, in the thoroughly-studied human genome version hg38: ERV-Hako, ERV-Saru, ERV-Hou, ERV-Han, and ERV-Goku. It also finds many relics of ERV-V, previously known from just two copies on chromosome 19 with placental genes. It finds a type of ERV flanked by MER41E long terminal repeats (LTRs), with surprisingly little similarity to the known MER41 ERV. ERV-Hako has subtypes that contain sequence from host genes SUSD6 and SPHKAP: the SUSD6 variant was transferred between catarrhine and platyrrhine primates. A retrovirus uses tRNA to prime reverse transcription: Hako is the only human ERV relic that used tRNA-Trp (tryptophan, symbol W), and HERV-W is misnamed because it used tRNA-Arg, based on the Genomic tRNA Database. One ERV-Saru LTR is the previously-described enhancer of AIM2 in innate immunity. This study contributes to understanding primate ERV history, but also shows that related ERVs can have drastic differences, challenging the goal of clearly annotating all ERV relics in genomes.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"11"},"PeriodicalIF":4.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625320","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":"Tandem LTR-retrotransposon structures are common and highly polymorphic in plant genomes.","authors":"Noemia Morales-Díaz, Svitlana Sushko, Lucía Campos-Dominguez, Venkataramana Kopalli, Agnieszka A Golicz, Raúl Castanera, Josep M Casacuberta","doi":"10.1186/s13100-025-00347-y","DOIUrl":"10.1186/s13100-025-00347-y","url":null,"abstract":"<p><strong>Background: </strong>LTR-retrotransposons (LTR-RT) are a major component of plant genomes and important drivers of genome evolution. Most LTR-RT copies in plant genomes are defective elements found as truncated copies, nested insertions or as part of more complex structures. The recent availability of highly contiguous plant genome assemblies based on long-read sequences now allows to perform detailed characterization of these complex structures and to evaluate their importance for plant genome evolution.</p><p><strong>Results: </strong>The detailed analysis of two rice loci containing complex LTR-RT structures showed that they consist of tandem arrays of LTR copies sharing internal LTRs. Our analyses suggests that these LTR-RT tandems are the result of a single insertion and not of the recombination of two independent LTR-RT elements. Our results also suggest that gypsy elements may be more prone to form these structures. We show that these structures are highly polymorphic in rice and therefore have the potential to generate genetic variability. We have developed a computational pipeline (IDENTAM) that scans genome sequences and identifies tandem LTR-RT candidates. Using this tool, we have detected 266 tandems in a pangenome built from the genomes of 76 accessions of cultivated and wild rice, showing that tandem LTR-RT structures are frequent and highly polymorphic in rice. Running IDENTAM in the Arabidopsis, almond and cotton genomes showed that LTR-RT tandems are frequent in plant genomes of different size, complexity and ploidy level. The complexity of differentiating intra-element variations at the nucleotide level among haplotypes is very high, and we found that graph-based pangenomic methodologies are appropriate to resolve these structures.</p><p><strong>Conclusions: </strong>Our results show that LTR-RT elements can form tandem arrays. These structures are relatively abundant and highly polymorphic in rice and are widespread in the plant kingdom. Future studies will contribute to understanding how these structures originate and whether the variability that they generate has a functional impact.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"10"},"PeriodicalIF":4.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616257","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":"Marine vs. terrestrial: links between the environment and the diversity of Copia retrotransposon in metazoans.","authors":"Khouloud Klai, Sarah Farhat, Laure Lamothe, Dominique Higuet, Éric Bonnivard","doi":"10.1186/s13100-025-00346-z","DOIUrl":"10.1186/s13100-025-00346-z","url":null,"abstract":"<p><strong>Background: </strong>LTR-retrotransposons are widely distributed among the eukaryote tree of life and have extensive impacts on genome evolution. Among the three canonical superfamilies, the Copia superfamily demonstrates the lowest abundances and repartitions among metazoans. To better understand their dynamics, we have conducted the first large-scale study of LTR-retrotransposon diversity in metazoans and we report on the diversity and distribution of the Copia elements.</p><p><strong>Results: </strong>We have identified over than 2,300 Copia elements from 263 metazoan genomes. The sequences were annotated at the clade level based on the classification of their RT/RNaseH domain. Our results confirmed that Copia are scarce in metazoans. However, we observed a great variation in Copia abundance between taxa. Surprisingly, some genomes, had a record number of copies, especially in Squamata. In contrast, terrestrial Deuterostomia display a clear loss of Copia diversity leading to their disappearance in some taxa. Additionally, we identified 18 new clades, tripling the number of previously defined clades. By studying more than 50 widespread taxa, we believe that most metazoan Copia clades have now been identified. The most striking result is that environment appears to be related to Copia distribution. We defined two sets of clades characterizing marine or terrestrial taxa. This two-sided pattern could be partially explained by horizontal transfers within both environments.</p><p><strong>Conclusions: </strong>This research enhances our understanding of transposable element evolution and emphasizes the influence of sharing the same ecological contexts on genomic diversity, and highlights the importance of annotating them at the clade level to characterize their evolutionary dynamics.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"9"},"PeriodicalIF":4.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586217","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 elements in genomic architecture of Monilinia fungal phytopathogens and TE-driven DMI-resistance adaptation.","authors":"Muhammed Raşit Durak, Hilal Özkılınç","doi":"10.1186/s13100-025-00343-2","DOIUrl":"10.1186/s13100-025-00343-2","url":null,"abstract":"<p><strong>Background: </strong>Fungicide resistance poses a significant challenge to plant disease management and influences the evolutionary dynamics of fungal pathogens. Besides being important phytopathogens, Monilinia species have become a model for discovering many fundamental questions related to fungal pathosystems. In this study, DMI-propiconazole sensitivity was investigated in view of transposable element (TE) dynamics in M. fructicola and M. laxa.</p><p><strong>Results: </strong>Propiconazole-sensitivity of 109 M. fructicola and 20 M. laxa isolates from different regions of Türkiye was assessed. Comprehensive TE identification within the species revealed that Class I elements were predominant, and TEs constituted approximately 9% of the genome for both M. fructicola and M. laxa, with a total of 15,327 and 10,710 TEs, respectively. An experimental evolution plan was developed for Monilinia that allows observing phenotypic and genotypic changes over successive generations under controlled selection pressures. Dynamic changes in TE content were discovered throughout the experimental evolution of M. fructicola under propiconazole pressure. With a net change of 187 TEs, the evolved strain showed an expansion of TE sequences, whereas different TE classes displayed diverse patterns of increase/decrease. Additionally, the presence of a nested TE upstream of the CYP51 gene was observed in less-sensitive M. fructicola isolates but absent in highly-sensitive ones. Gene expressions of CYP51 differed significantly between TE-containing and TE-lacking isolates, strongly supporting the contribution of this TE to fungicide resistance.</p><p><strong>Conclusion: </strong>This study establishes a critical link between TEs and DMI fungicide resistance by associating a nested TE with reduced sensitivity to propiconazole. We introduce an innovative experimental evolution framework for studying genomic changes under selective pressure and provide a comprehensive characterization of Monilinia TEs. These findings significantly advance our understanding of molecular resistance mechanisms in fungal pathogens, offering insights for more effective disease management.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"8"},"PeriodicalIF":4.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586303","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":"On the origin of the P-element invasion in Drosophila simulans.","authors":"Filip Wierzbicki, Riccardo Pianezza, Divya Selvaraju, Madeleine Maria Eller, Robert Kofler","doi":"10.1186/s13100-025-00345-0","DOIUrl":"10.1186/s13100-025-00345-0","url":null,"abstract":"<p><p>The horizontal transfer (HT) of the P-element is one of the best documented cases of the HT of a transposable element. The P-element invaded natural D. melanogaster populations between 1950 and 1980 following its HT from Drosophila willistoni, a species endemic to South and Central America. Subsequently, it spread in D. simulans populations between 2006 and 2014, following a HT from D. melanogaster. The geographic region where the spread into D. simulans occurred is unclear, as both involved species are cosmopolitan. The P-element differs between these two species by a single base substitution at site 2040, where D. melanogaster carries a 'G' and D. simulans carries an 'A'. It has been hypothesized that this base substitution was a necessary adaptation that enabled the spread of the P-element in D. simulans, potentially explaining the 30-50-year lag between the invasions of D. melanogaster and D. simulans. To test this hypothesis, we monitored the invasion dynamics of P-elements with both alleles in experimental populations of D. melanogaster and D. simulans. Our results indicate that the allele at site 2040 has a minimal impact on the invasion dynamics of the P-element and, therefore, was not necessary for the invasion of D. simulans. However, we found that the host species significantly influenced the invasion dynamics, with higher P-element copy numbers accumulating in D. melanogaster than in D. simulans. Finally, based on SNPs segregating in natural D. melanogaster populations, we suggest that the horizontal transfer of the P-element from D. melanogaster to D. simulans likely occurred around Tasmania.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"7"},"PeriodicalIF":4.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516163","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":"Alternative splicing of transposable elements in human breast cancer.","authors":"Alex Nesta, Diogo F T Veiga, Jacques Banchereau, Olga Anczukow, Christine R Beck","doi":"10.1186/s13100-025-00341-4","DOIUrl":"10.1186/s13100-025-00341-4","url":null,"abstract":"<p><p>Transposable elements (TEs) drive genome evolution and can affect gene expression through diverse mechanisms. In breast cancer, disrupted regulation of TE sequences may facilitate tumor-specific transcriptomic alterations. We examine 142,514 full-length isoforms derived from long-read RNA sequencing (LR-seq) of 30 breast samples to investigate the effects of TEs on the breast cancer transcriptome. Approximately half of these isoforms contain TE sequences, and these contribute to half of the novel annotated splice junctions. We quantify splicing of these LR-seq derived isoforms in 1,135 breast tumors from The Cancer Genome Atlas (TCGA) and 1,329 healthy tissue samples from the Genotype-Tissue Expression (GTEx), and find 300 TE-overlapping tumor-specific splicing events. Some splicing events are enriched in specific breast cancer subtypes - for example, a TE-driven transcription start site upstream of ERBB2 in HER2 + tumors, and several TE-mediated splicing events are associated with patient survival and poor prognosis. The full-length sequences we capture with LR-seq reveal thousands of isoforms with signatures of RNA editing, including a novel isoform belonging to RHOA; a gene previously implicated in tumor progression. We utilize our full-length isoforms to discover polymorphic TE insertions that alter splicing and validate one of these events in breast cancer cell lines. Together, our results demonstrate the widespread effects of dysregulated TEs on breast cancer transcriptomes and highlight the advantages of long-read isoform sequencing for understanding TE biology. TE-derived isoforms may alter the expression of genes important in cancer and can potentially be used as novel, disease-specific therapeutic targets or biomarkers.One sentence summary: Transposable elements generate alternative isoforms and alter post-transcriptional regulation in human breast cancer.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"16 1","pages":"6"},"PeriodicalIF":4.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476766","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}