{"title":"CRISPR-TE: a web-based tool to generate single guide RNAs targeting transposable elements","authors":"Yixin Guo, Ziwei Xue, Meiting Gong, Siqian Jin, Xindi Wu, Wanlu Liu","doi":"10.1186/s13100-024-00313-0","DOIUrl":"https://doi.org/10.1186/s13100-024-00313-0","url":null,"abstract":"The CRISPR/Cas systems have emerged as powerful tools in genome engineering. Recent studies highlighting the crucial role of transposable elements (TEs) have stimulated research interest in manipulating these elements to understand their functions. However, designing single guide RNAs (sgRNAs) that are specific and efficient for TE manipulation is a significant challenge, given their sequence repetitiveness and high copy numbers. While various sgRNA design tools have been developed for gene editing, an optimized sgRNA designer for TE manipulation has yet to be established. We present CRISPR-TE, a web-based application featuring an accessible graphical user interface, available at https://www.crisprte.cn/ , and currently tailored to the human and mouse genomes. CRISPR-TE identifies all potential sgRNAs for TEs and provides a comprehensive solution for efficient TE targeting at both the single copy and subfamily levels. Our analysis shows that sgRNAs targeting TEs can more effectively target evolutionarily young TEs with conserved sequences at the subfamily level. CRISPR-TE offers a versatile framework for designing sgRNAs for TE targeting. CRISPR-TE is publicly accessible at https://www.crisprte.cn/ as an online web service and the source code of CRISPR-TE is available at https://github.com/WanluLiuLab/CRISPRTE/ .","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"67 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139656551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-01-20DOI: 10.1186/s13100-024-00312-1
Ursula Oggenfuss, Thomas Badet, Daniel Croll
{"title":"A systematic screen for co-option of transposable elements across the fungal kingdom","authors":"Ursula Oggenfuss, Thomas Badet, Daniel Croll","doi":"10.1186/s13100-024-00312-1","DOIUrl":"https://doi.org/10.1186/s13100-024-00312-1","url":null,"abstract":"How novel protein functions are acquired is a central question in molecular biology. Key paths to novelty include gene duplications, recombination or horizontal acquisition. Transposable elements (TEs) are increasingly recognized as a major source of novel domain-encoding sequences. However, the impact of TE coding sequences on the evolution of the proteome remains understudied. Here, we analyzed 1237 genomes spanning the phylogenetic breadth of the fungal kingdom. We scanned proteomes for evidence of co-occurrence of TE-derived domains along with other conventional protein functional domains. We detected more than 13,000 predicted proteins containing potentially TE-derived domain, of which 825 were identified in more than five genomes, indicating that many host-TE fusions may have persisted over long evolutionary time scales. We used the phylogenetic context to identify the origin and retention of individual TE-derived domains. The most common TE-derived domains are helicases derived from Academ, Kolobok or Helitron. We found putative TE co-options at a higher rate in genomes of the Saccharomycotina, providing an unexpected source of protein novelty in these generally TE depleted genomes. We investigated in detail a candidate host-TE fusion with a heterochromatic transcriptional silencing function that may play a role in TE and gene regulation in ascomycetes. The affected gene underwent multiple full or partial losses within the phylum. Overall, our work establishes a kingdom-wide view of putative host-TE fusions and facilitates systematic investigations of candidate fusion proteins.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"42 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139508038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2024-01-13DOI: 10.1186/s13100-023-00311-8
Ivar Westerberg, S. Lorena Ament-Velásquez, Aaron A. Vogan, Hanna Johannesson
{"title":"Evolutionary dynamics of the LTR-retrotransposon crapaud in the Podospora anserina species complex and the interaction with repeat-induced point mutations","authors":"Ivar Westerberg, S. Lorena Ament-Velásquez, Aaron A. Vogan, Hanna Johannesson","doi":"10.1186/s13100-023-00311-8","DOIUrl":"https://doi.org/10.1186/s13100-023-00311-8","url":null,"abstract":"The genome of the filamentous ascomycete Podospora anserina shows a relatively high abundance of retrotransposons compared to other interspersed repeats. The LTR-retrotransposon family crapaud is particularly abundant in the genome, and consists of multiple diverged sequence variations specifically localized in the 5’ half of both long terminal repeats (LTRs). P. anserina is part of a recently diverged species-complex, which makes the system ideal to classify the crapaud family based on the observed LTR variation and to study the evolutionary dynamics, such as the diversification and bursts of the elements over recent evolutionary time. We developed a sequence similarity network approach to classify the crapaud repeats of seven genomes representing the P. anserina species complex into 14 subfamilies. This method does not utilize a consensus sequence, but instead it connects any copies that share enough sequence similarity over a set sequence coverage. Based on phylogenetic analyses, we found that the crapaud repeats likely diversified in the ancestor of the complex and have had activity at different time points for different subfamilies. Furthermore, while we hypothesized that the evolution into multiple subfamilies could have been a direct effect of escaping the genome defense system of repeat induced point mutations, we found this not to be the case. Our study contributes to the development of methods to classify transposable elements in fungi, and also highlights the intricate patterns of retrotransposon evolution over short timescales and under high mutational load caused by nucleotide-altering genome defense.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"127 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139464392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2023-12-12DOI: 10.1186/s13100-023-00310-9
Kenji Ichiyanagi, Yoko Ikeda, Kuniaki Saito
{"title":"The sixth Japanese meeting on biological function and evolution through interactions between hosts and transposable elements","authors":"Kenji Ichiyanagi, Yoko Ikeda, Kuniaki Saito","doi":"10.1186/s13100-023-00310-9","DOIUrl":"https://doi.org/10.1186/s13100-023-00310-9","url":null,"abstract":"The sixth Japanese meeting on host–transposon interactions, titled “Biological Function and Evolution through Interactions between Hosts and Transposable Elements,” was held on August 24th and 25th, 2023, at the National Institute of Genetics as well as online. This meeting was supported by the National Institute of Genetics and aimed to bring together researchers studying the diverse roles of TEs in genome function and evolution, as well as host defense systems against TE mobility, TE bursts during evolution, and intron mobility in mammals, insects, land plants, yeast, protozoa, and bacteria. Here, we have presented the highlights of the discussion. Organizers: Kenji Ichiyanagi, Yoko Ikeda, and Kuniaki Saito.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138575434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2023-12-07DOI: 10.1186/s13100-023-00309-2
Nikita S. Vassetzky, Sergei A. Kosushkin, Alexey P. Ryskov
{"title":"SINE-derived satellites in scaled reptiles","authors":"Nikita S. Vassetzky, Sergei A. Kosushkin, Alexey P. Ryskov","doi":"10.1186/s13100-023-00309-2","DOIUrl":"https://doi.org/10.1186/s13100-023-00309-2","url":null,"abstract":"The genomes of many eukaryotes contain DNA repeats in the form of both tandem and interspersed elements with distinct structure, evolutionary histories, and mechanisms of emergence and amplification. Although there is considerable knowledge regarding their diversity, there is little evidence directly linking these two types. Different tandem repeats derived from portions of short interspersed elements (SINEs) belonging to different families were identified in 56 genomes of squamate reptiles. All loci of SINE-derived satellites (sSats) were thoroughly analyzed. Snake sSats exhibited high similarity in both structure and copy number, while other taxa may have highly diverse (geckos), rare (Darevskia lizards), or missing sSats (agamid lizards). Similar to most satellites associated with heterochromatin, sSats are likely linked to subtelomeric chromosomal regions. Discovered tandem repeats derived from SINEs exhibit satellite-like properties, although they have not amplified to the same degree as typical satellites. The autonomous emergence of distinct sSats from diverse SINE families in numerous squamate species suggests a nonrandom process of satellite genesis originating from repetitive SINEs.","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"39 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138548434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mobile DNAPub Date : 2023-11-30DOI: 10.1186/s13100-023-00308-3
Carmen A Buttler, Daniel Ramirez, Robin D Dowell, Edward B Chuong
{"title":"An intronic LINE-1 regulates IFNAR1 expression in human immune cells.","authors":"Carmen A Buttler, Daniel Ramirez, Robin D Dowell, Edward B Chuong","doi":"10.1186/s13100-023-00308-3","DOIUrl":"10.1186/s13100-023-00308-3","url":null,"abstract":"<p><strong>Background: </strong>Despite their origins as selfish parasitic sequences, some transposons in the human genome have been co-opted to serve as regulatory elements, contributing to the evolution of transcriptional networks. Most well-characterized examples of transposon-derived regulatory elements derive from endogenous retroviruses (ERVs), due to the intrinsic regulatory activity of proviral long terminal repeat regions. However, one subclass of transposable elements, the Long Interspersed Nuclear Elements (LINEs), have been largely overlooked in the search for functional regulatory transposons, and considered to be broadly epigenetically repressed.</p><p><strong>Results: </strong>We examined the chromatin state of LINEs by analyzing epigenomic data from human immune cells. Many LINEs are marked by the repressive H3K9me3 modification, but a subset exhibits evidence of enhancer activity in human immune cells despite also showing evidence of epigenetic repression. We hypothesized that these competing forces of repressive and activating epigenetic marks might lead to inducible enhancer activity. We investigated a specific L1M2a element located within the first intron of Interferon Alpha/Beta Receptor 1 (IFNAR1). This element shows epigenetic signatures of B cell-specific enhancer activity, despite being repressed by the Human Silencing Hub (HUSH) complex. CRISPR deletion of the element in B lymphoblastoid cells revealed that the element acts as an enhancer that regulates both steady state and interferon-inducible expression of IFNAR1.</p><p><strong>Conclusions: </strong>Our study experimentally demonstrates that an L1M2a element was co-opted to function as an interferon-inducible enhancer of IFNAR1, creating a feedback loop wherein IFNAR1 is transcriptionally upregulated by interferon signaling. This finding suggests that other LINEs may exhibit cryptic cell type-specific or context-dependent enhancer activity. LINEs have received less attention than ERVs in the effort to understand the contribution of transposons to the regulatory landscape of cellular genomes, but these are likely important, lineage-specific players in the rapid evolution of immune system regulatory networks and deserve further study.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"20"},"PeriodicalIF":4.9,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138461002","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}
Mobile DNAPub Date : 2023-11-27DOI: 10.1186/s13100-023-00307-4
Irina R Arkhipova, Kathleen H Burns, Katherine B Chiappinelli, Edward B Chuong, Clement Goubert, Alba Guarné, Amanda M Larracuente, E Alice Lee, Henry L Levin
{"title":"Meeting report: transposable elements at the crossroads of evolution, health and disease 2023.","authors":"Irina R Arkhipova, Kathleen H Burns, Katherine B Chiappinelli, Edward B Chuong, Clement Goubert, Alba Guarné, Amanda M Larracuente, E Alice Lee, Henry L Levin","doi":"10.1186/s13100-023-00307-4","DOIUrl":"10.1186/s13100-023-00307-4","url":null,"abstract":"<p><p>The conference \"Transposable Elements at the Crossroads of Evolution, Health and Disease\" was hosted by Keystone Symposia in Whistler, British Columbia, Canada, on September 3-6, 2023, and was organized by Kathleen Burns, Harmit Malik and Irina Arkhipova. The central theme of the meeting was the incredible diversity of ways in which transposable elements (TEs) interact with the host, from disrupting the existing genes and pathways to creating novel gene products and expression patterns, enhancing the repertoire of host functions, and ultimately driving host evolution. The meeting was organized into six plenary sessions and two afternoon workshops with a total of 50 invited and contributed talks, two poster sessions, and a career roundtable. The topics ranged from TE roles in normal and pathological processes to restricting and harnessing TE activity based on mechanistic insights gained from genetic, structural, and biochemical studies.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"19"},"PeriodicalIF":4.7,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445492","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}
Mobile DNAPub Date : 2023-11-21DOI: 10.1186/s13100-023-00306-5
Jef D Boeke, Kathleen H Burns, Katherine B Chiappinelli, Marie Classon, John M Coffin, Daniel D DeCarvalho, Joseph D Dukes, Benjamin Greenbaum, George Kassiotis, Sarah K Knutson, Arnold J Levine, Avindra Nath, Sophie Papa, Daniel Rios, John Sedivy, David T Ting
{"title":"Proceedings of the inaugural Dark Genome Symposium: November 2022.","authors":"Jef D Boeke, Kathleen H Burns, Katherine B Chiappinelli, Marie Classon, John M Coffin, Daniel D DeCarvalho, Joseph D Dukes, Benjamin Greenbaum, George Kassiotis, Sarah K Knutson, Arnold J Levine, Avindra Nath, Sophie Papa, Daniel Rios, John Sedivy, David T Ting","doi":"10.1186/s13100-023-00306-5","DOIUrl":"10.1186/s13100-023-00306-5","url":null,"abstract":"<p><p>In November 2022 the first Dark Genome Symposium was held in Boston, USA. The meeting was hosted by Rome Therapeutics and Enara Bio, two biotechnology companies working on translating our growing understanding of this vast genetic landscape into therapies for human disease. The spirit and ambition of the meeting was one of shared knowledge, looking to strengthen the network of researchers engaged in the field. The meeting opened with a welcome from Rosana Kapeller and Kevin Pojasek followed by a first session of field defining talks from key academics in the space. A series of panels, bringing together academia and industry views, were then convened covering a wide range of pertinent topics. Finally, Richard Young and David Ting gave their views on the future direction and promise for patient impact inherent in the growing understanding of the Dark Genome.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"18"},"PeriodicalIF":4.7,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291407","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}
Mobile DNAPub Date : 2023-11-15DOI: 10.1186/s13100-023-00305-6
Jiangzhao Qian, Heba M M Ibrahim, Myriam Erz, Florian Kümmel, Ralph Panstruga, Stefan Kusch
{"title":"Long noncoding RNAs emerge from transposon-derived antisense sequences and may contribute to infection stage-specific transposon regulation in a fungal phytopathogen.","authors":"Jiangzhao Qian, Heba M M Ibrahim, Myriam Erz, Florian Kümmel, Ralph Panstruga, Stefan Kusch","doi":"10.1186/s13100-023-00305-6","DOIUrl":"10.1186/s13100-023-00305-6","url":null,"abstract":"<p><strong>Background: </strong>The genome of the obligate biotrophic phytopathogenic barley powdery mildew fungus Blumeria hordei is inflated due to highly abundant and possibly active transposable elements (TEs). In the absence of the otherwise common repeat-induced point mutation transposon defense mechanism, noncoding RNAs could be key for regulating the activity of TEs and coding genes during the pathogenic life cycle.</p><p><strong>Results: </strong>We performed time-course whole-transcriptome shotgun sequencing (RNA-seq) of total RNA derived from infected barley leaf epidermis at various stages of fungal pathogenesis and observed significant transcript accumulation and time point-dependent regulation of TEs in B. hordei. Using a manually curated consensus database of 344 TEs, we discovered phased small RNAs mapping to 104 consensus transposons, suggesting that RNA interference contributes significantly to their regulation. Further, we identified 5,127 long noncoding RNAs (lncRNAs) genome-wide in B. hordei, of which 823 originated from the antisense strand of a TE. Co-expression network analysis of lncRNAs, TEs, and coding genes throughout the asexual life cycle of B. hordei points at extensive positive and negative co-regulation of lncRNAs, subsets of TEs and coding genes.</p><p><strong>Conclusions: </strong>Our work suggests that similar to mammals and plants, fungal lncRNAs support the dynamic modulation of transcript levels, including TEs, during pivotal stages of host infection. The lncRNAs may support transcriptional diversity and plasticity amid loss of coding genes in powdery mildew fungi and may give rise to novel regulatory elements and virulence peptides, thus representing key drivers of rapid evolutionary adaptation to promote pathogenicity and overcome host defense.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"17"},"PeriodicalIF":4.9,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10648671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591771","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}
Mobile DNAPub Date : 2023-10-20DOI: 10.1186/s13100-023-00303-8
Nikola A Mizgier, Charlie E Jones, Anthony V Furano
{"title":"Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement.","authors":"Nikola A Mizgier, Charlie E Jones, Anthony V Furano","doi":"10.1186/s13100-023-00303-8","DOIUrl":"10.1186/s13100-023-00303-8","url":null,"abstract":"<p><p>L1 (LINE1) non-LTR retrotransposons are ubiquitous genomic parasites and the dominant transposable element in humans having generated about 40% of their genomic DNA during their ~ 100 million years (Myr) of activity in primates. L1 replicates in germ line cells and early embryos, causing genetic diversity and defects, but can be active in some somatic stem cells, tumors and during aging. L1 encodes two proteins essential for retrotransposition: ORF2p, a reverse transcriptase that contains an endonuclease domain, and ORF1p, a coiled coil mediated homo trimer, which functions as a nucleic acid chaperone. Both proteins contain highly conserved domains and preferentially bind their encoding transcript to form an L1 ribonucleoprotein (RNP), which mediates retrotransposition. However, the coiled coil has periodically undergone episodes of substantial amino acid replacement to the extent that a given L1 family can concurrently express multiple ORF1s that differ in the sequence of their coiled coils. Here we show that such distinct ORF1p sequences can become entangled forming heterotrimers when co-expressed from separate vectors and speculate on how coiled coil entanglement could affect coiled coil evolution.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"16"},"PeriodicalIF":4.9,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49679845","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}