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Transposable Elements II
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Transposable Elements II

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 35839

Special Issue Editors

Prof. Dr. Teresa Capriglione

E-Mail Website
Guest Editor
Dipartimento di Biologia, Università di Napoli "Federico II", Complesso Universitario di Monte S. Angelo, Via Cinthia, 80126 Napoli, Italy
Interests: PCR; DNA; cloning; molecular biology; RNA; DNA sequencing; molecular genetics; genomics sequencing; molecular cloning; bioinformatics; phylogenetic analysis; chromosomes; gene expression and chromatin biology; microsatellites; cytogenetics; in situ hybridization; developmental neuroscience; hybridization; developmental genetics; vertebrates; southern blot; Y chromosome; centromere; polyploidy; transposable elements; transposons; mIRBase
Special Issues, Collections and Topics in MDPI journals
Dr. Anna Maria Pappalardo

E-Mail Website
Guest Editor
Dipartimento di Scienze Biologiche, Geologiche e Ambientali, Sez. di Biologia Animale “M. La Greca”, Università di Catania, Via Androne 81, 95124 Catania, Italy
Interests: DNA; PCR; DNA sequencing; molecular evolution; DNA barcoding; molecular phylogenetics; population genetics; marine biology; teleosts; biomarker of environmental pollution; molecular marker; food traceability; molecular species identification; transposable elements; cell biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Transposable elements are discrete DNA sequences ubiquitous among prokaryotic and eukaryotic genomes. The ability to self-replicate and move within and among chromosomes, inserting in both coding and noncoding regions, makes transposable elements particularly important for genome functionality and evolution. Transposable elements were first discovered nearly 70 years ago and considered mostly deleterious for host genomes—a kind of genomic parasite. Despite their selfish nature, later studies indicated their high natural abundance within genomes (up to 50% in some instances) and their implications for genome evolution.

Nowadays, the implication of transposable elements in many biological processes is well known, including speciation, adaptation, horizontal transfer, and pathological conditions in humans. At the genome level, transposable elements are currently recognized as a powerful source of genetic variation, genomic restructuring, and gene expression modulation. Moreover, a growing body of evidence highlights events of exaptation, in which transposable element sequences have been “recruited” by host genomes and integrated in gene structures and/or gene regulatory networks. Transposable elements have even been found to play a role in development, neurogenesis, and aging.

In recent years, the use of transposable elements as a means of genomic modification and transgenesis has been envisaged and effectively put into practice. Today, some engineered transposable elements are used for gene transfer therapy.

In the current “genomic era”, in which NGS technologies allow the sequencing and assembly of many genomes and transcriptomes, studies of transposable elements have been boosted by the huge quantity of available sequence information. Therefore, we are currently in an exciting moment for transposable element studies! The present Special Issue aims to gather current knowledge from past studies and from cutting-edge transposable element research through selected papers on hot topics of transposable element biology. Therefore, studies based on experimental evidence, suggesting or updating evolutionary models, and dealing with applications are well suited for this Special Issue.

The Guest Editor Prof. Dr. Teresa Capriglione passed away after a battle with her illness.

Prof. Dr. Teresa Capriglione

Dr. Anna Maria Pappalardo

Guest Editors

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Keywords

  • transposon
  • jumping gene
  • retrotransposon
  • DNA transposon
  • endogenous retrovirus
  • reverse transcription
  • integration
  • host
  • genome evolution
  • genomic modification
  • gene structure
  • disease

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Published Papers (7 papers)

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Research

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17 pages, 3396 KiB  
Article
Functional Characterization of the N-Terminal Disordered Region of the piggyBac Transposase
by Gerda Wachtl, Éva Schád, Krisztina Huszár, Antonio Palazzo, Zoltán Ivics, Ágnes Tantos and Tamás I. Orbán
Int. J. Mol. Sci. 2022, 23(18), 10317; https://doi.org/10.3390/ijms231810317 - 7 Sep 2022
Cited by 2 | Viewed by 2377
Abstract
The piggyBac DNA transposon is an active element initially isolated from the cabbage looper moth, but members of this superfamily are also present in most eukaryotic evolutionary lineages. The functionally important regions of the transposase are well described. There is an RNase H-like [...] Read more.
The piggyBac DNA transposon is an active element initially isolated from the cabbage looper moth, but members of this superfamily are also present in most eukaryotic evolutionary lineages. The functionally important regions of the transposase are well described. There is an RNase H-like fold containing the DDD motif responsible for the catalytic DNA cleavage and joining reactions and a C-terminal cysteine-rich domain important for interaction with the transposon DNA. However, the protein also contains a ~100 amino acid long N-terminal disordered region (NTDR) whose function is currently unknown. Here we show that deletion of the NTDR significantly impairs piggyBac transposition, although the extent of decrease is strongly cell-type specific. Moreover, replacing the NTDR with scrambled but similarly disordered sequences did not rescue transposase activity, indicating the importance of sequence conservation. Cell-based transposon excision and integration assays reveal that the excision step is more severely affected by NTDR deletion. Finally, bioinformatic analyses indicated that the NTDR is specific for the piggyBac superfamily and is also present in domesticated, transposase-derived proteins incapable of catalyzing transposition. Our results indicate an essential role of the NTDR in the “fine-tuning” of transposition and its significance in the functions of piggyBac-originated co-opted genes. Full article
(This article belongs to the Special Issue Transposable Elements II)
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13 pages, 1874 KiB  
Article
Engineered Sleeping Beauty Transposon as Efficient System to Optimize Chimp Adenoviral Production
by Samantha Baldassarri, Daniela Benati, Federica D’Alessio, Clarissa Patrizi, Eleonora Cattin, Michela Gentile, Angelo Raggioli and Alessandra Recchia
Int. J. Mol. Sci. 2022, 23(14), 7538; https://doi.org/10.3390/ijms23147538 - 7 Jul 2022
Cited by 1 | Viewed by 2448
Abstract
Sleeping Beauty (SB) is the first DNA transposon employed for efficient transposition in vertebrate cells, opening new applications for genetic engineering and gene therapies. A transposon-based gene delivery system holds the favourable features of non-viral vectors and an attractive safety profile. Here, we [...] Read more.
Sleeping Beauty (SB) is the first DNA transposon employed for efficient transposition in vertebrate cells, opening new applications for genetic engineering and gene therapies. A transposon-based gene delivery system holds the favourable features of non-viral vectors and an attractive safety profile. Here, we employed SB to engineer HEK293 cells for optimizing the production of a chimpanzee Adenovector (chAd) belonging to the Human Mastadenovirus C species. To date, chAd vectors are employed in several clinical settings for infectious diseases, last but not least COVID-19. A robust, efficient and quick viral vector production could advance the clinical application of chAd vectors. To this aim, we firstly swapped the hAd5 E1 with chAd-C E1 gene by using the CRISPR/Cas9 system. We demonstrated that in the absence of human Ad5 E1, chimp Ad-C E1 gene did not support HEK293 survival. To improve chAd-C vector production, we engineered HEK293 cells to stably express the chAd-C precursor terminal protein (ch.pTP), which plays a crucial role in chimpanzee Adenoviral DNA replication. The results indicate that exogenous ch.pTP expression significantly ameliorate the packaging and amplification of recombinant chAd-C vectors thus, the engineered HEK293ch.pTP cells could represent a superior packaging cell line for the production of these vectors. Full article
(This article belongs to the Special Issue Transposable Elements II)
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20 pages, 5088 KiB  
Article
Complex Genetic Interactions between Piwi and HP1a in the Repression of Transposable Elements and Tissue-Specific Genes in the Ovarian Germline
by Artem A. Ilyin, Anastasia D. Stolyarenko, Nikolay Zenkin and Mikhail S. Klenov
Int. J. Mol. Sci. 2021, 22(24), 13430; https://doi.org/10.3390/ijms222413430 - 14 Dec 2021
Cited by 3 | Viewed by 2893
Abstract
Insertions of transposable elements (TEs) in eukaryotic genomes are usually associated with repressive chromatin, which spreads to neighbouring genomic sequences. In ovaries of Drosophila melanogaster, the Piwi-piRNA pathway plays a key role in the transcriptional silencing of TEs considered to be exerted [...] Read more.
Insertions of transposable elements (TEs) in eukaryotic genomes are usually associated with repressive chromatin, which spreads to neighbouring genomic sequences. In ovaries of Drosophila melanogaster, the Piwi-piRNA pathway plays a key role in the transcriptional silencing of TEs considered to be exerted mostly through the establishment of H3K9me3 histone marks recruiting Heterochromatin Protein 1a (HP1a). Here, using RNA-seq, we investigated the expression of TEs and the adjacent genomic regions upon Piwi and HP1a germline knockdowns sharing a similar genetic background. We found that the depletion of Piwi and HP1a led to the derepression of only partially overlapping TE sets. Several TEs were silenced predominantly by HP1a, whereas the upregulation of some other TEs was more pronounced upon Piwi knockdown and, surprisingly, was diminished upon a Piwi/HP1a double-knockdown. We revealed that HP1a loss influenced the expression of thousands of protein-coding genes mostly not adjacent to TE insertions and, in particular, downregulated a putative transcriptional factor required for TE activation. Nevertheless, our results indicate that Piwi and HP1a cooperatively exert repressive effects on the transcription of euchromatic loci flanking the insertions of some Piwi-regulated TEs. We suggest that this mechanism controls the silencing of a small set of TE-adjacent tissue-specific genes, preventing their inappropriate expression in ovaries. Full article
(This article belongs to the Special Issue Transposable Elements II)
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21 pages, 2817 KiB  
Article
Widespread Exaptation of L1 Transposons for Transcription Factor Binding in Breast Cancer
by Jiayue-Clara Jiang, Joseph A. Rothnagel and Kyle R. Upton
Int. J. Mol. Sci. 2021, 22(11), 5625; https://doi.org/10.3390/ijms22115625 - 25 May 2021
Cited by 5 | Viewed by 3548
Abstract
L1 transposons occupy 17% of the human genome and are widely exapted for the regulation of human genes, particularly in breast cancer, where we have previously shown abundant cancer-specific transcription factor (TF) binding sites within the L1PA2 subfamily. In the current study, we [...] Read more.
L1 transposons occupy 17% of the human genome and are widely exapted for the regulation of human genes, particularly in breast cancer, where we have previously shown abundant cancer-specific transcription factor (TF) binding sites within the L1PA2 subfamily. In the current study, we performed a comprehensive analysis of TF binding activities in primate-specific L1 subfamilies and identified pervasive exaptation events amongst these evolutionarily related L1 transposons. By motif scanning, we predicted diverse and abundant TF binding potentials within the L1 transposons. We confirmed substantial TF binding activities in the L1 subfamilies using TF binding sites consolidated from an extensive collection of publicly available ChIP-seq datasets. Young L1 subfamilies (L1HS, L1PA2 and L1PA3) contributed abundant TF binding sites in MCF7 cells, primarily via their 5′ UTR. This is expected as the L1 5′ UTR hosts cis-regulatory elements that are crucial for L1 replication and mobilisation. Interestingly, the ancient L1 subfamilies, where 5′ truncation was common, displayed comparable TF binding capacity through their 3′ ends, suggesting an alternative exaptation mechanism in L1 transposons that was previously unnoticed. Overall, primate-specific L1 transposons were extensively exapted for TF binding in MCF7 breast cancer cells and are likely prominent genetic players modulating breast cancer transcriptional regulation. Full article
(This article belongs to the Special Issue Transposable Elements II)
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12 pages, 1928 KiB  
Article
Transposable Elements and Teleost Migratory Behaviour
by Elisa Carotti, Federica Carducci, Adriana Canapa, Marco Barucca, Samuele Greco, Marco Gerdol and Maria Assunta Biscotti
Int. J. Mol. Sci. 2021, 22(2), 602; https://doi.org/10.3390/ijms22020602 - 9 Jan 2021
Cited by 12 | Viewed by 3112
Abstract
Transposable elements (TEs) represent a considerable fraction of eukaryotic genomes, thereby contributing to genome size, chromosomal rearrangements, and to the generation of new coding genes or regulatory elements. An increasing number of works have reported a link between the genomic abundance of TEs [...] Read more.
Transposable elements (TEs) represent a considerable fraction of eukaryotic genomes, thereby contributing to genome size, chromosomal rearrangements, and to the generation of new coding genes or regulatory elements. An increasing number of works have reported a link between the genomic abundance of TEs and the adaptation to specific environmental conditions. Diadromy represents a fascinating feature of fish, protagonists of migratory routes between marine and freshwater for reproduction. In this work, we investigated the genomes of 24 fish species, including 15 teleosts with a migratory behaviour. The expected higher relative abundance of DNA transposons in ray-finned fish compared with the other fish groups was not confirmed by the analysis of the dataset considered. The relative contribution of different TE types in migratory ray-finned species did not show clear differences between oceanodromous and potamodromous fish. On the contrary, a remarkable relationship between migratory behaviour and the quantitative difference reported for short interspersed nuclear (retro)elements (SINEs) emerged from the comparison between anadromous and catadromous species, independently from their phylogenetic position. This aspect is likely due to the substantial environmental changes faced by diadromous species during their migratory routes. Full article
(This article belongs to the Special Issue Transposable Elements II)
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Review

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29 pages, 3014 KiB  
Review
Contemporary Transposon Tools: A Review and Guide through Mechanisms and Applications of Sleeping Beauty, piggyBac and Tol2 for Genome Engineering
by Nicolás Sandoval-Villegas, Wasifa Nurieva, Maximilian Amberger and Zoltán Ivics
Int. J. Mol. Sci. 2021, 22(10), 5084; https://doi.org/10.3390/ijms22105084 - 11 May 2021
Cited by 69 | Viewed by 14959
Abstract
Transposons are mobile genetic elements evolved to execute highly efficient integration of their genes into the genomes of their host cells. These natural DNA transfer vehicles have been harnessed as experimental tools for stably introducing a wide variety of foreign DNA sequences, including [...] Read more.
Transposons are mobile genetic elements evolved to execute highly efficient integration of their genes into the genomes of their host cells. These natural DNA transfer vehicles have been harnessed as experimental tools for stably introducing a wide variety of foreign DNA sequences, including selectable marker genes, reporters, shRNA expression cassettes, mutagenic gene trap cassettes, and therapeutic gene constructs into the genomes of target cells in a regulated and highly efficient manner. Given that transposon components are typically supplied as naked nucleic acids (DNA and RNA) or recombinant protein, their use is simple, safe, and economically competitive. Thus, transposons enable several avenues for genome manipulations in vertebrates, including transgenesis for the generation of transgenic cells in tissue culture comprising the generation of pluripotent stem cells, the production of germline-transgenic animals for basic and applied research, forward genetic screens for functional gene annotation in model species and therapy of genetic disorders in humans. This review describes the molecular mechanisms involved in transposition reactions of the three most widely used transposon systems currently available (Sleeping Beauty, piggyBac, and Tol2), and discusses the various parameters and considerations pertinent to their experimental use, highlighting the state-of-the-art in transposon technology in diverse genetic applications. Full article
(This article belongs to the Special Issue Transposable Elements II)
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Graphical abstract

16 pages, 1906 KiB  
Review
Transposable Elements and Stress in Vertebrates: An Overview
by Anna Maria Pappalardo, Venera Ferrito, Maria Assunta Biscotti, Adriana Canapa and Teresa Capriglione
Int. J. Mol. Sci. 2021, 22(4), 1970; https://doi.org/10.3390/ijms22041970 - 17 Feb 2021
Cited by 26 | Viewed by 4938
Abstract
Since their identification as genomic regulatory elements, Transposable Elements (TEs) were considered, at first, molecular parasites and later as an important source of genetic diversity and regulatory innovations. In vertebrates in particular, TEs have been recognized as playing an important role in major [...] Read more.
Since their identification as genomic regulatory elements, Transposable Elements (TEs) were considered, at first, molecular parasites and later as an important source of genetic diversity and regulatory innovations. In vertebrates in particular, TEs have been recognized as playing an important role in major evolutionary transitions and biodiversity. Moreover, in the last decade, a significant number of papers has been published highlighting a correlation between TE activity and exposition to environmental stresses and dietary factors. In this review we present an overview of the impact of TEs in vertebrate genomes, report the silencing mechanisms adopted by host genomes to regulate TE activity, and finally we explore the effects of environmental and dietary factor exposures on TE activity in mammals, which is the most studied group among vertebrates. The studies here reported evidence that several factors can induce changes in the epigenetic status of TEs and silencing mechanisms leading to their activation with consequent effects on the host genome. The study of TE can represent a future challenge for research for developing effective markers able to detect precocious epigenetic changes and prevent human diseases. Full article
(This article belongs to the Special Issue Transposable Elements II)
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