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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 January 2020) | Viewed by 63958

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Prof. Dr. Teresa Capriglione

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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
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Prof. Dr. Andrea Luchetti

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MoZoo Lab, Department of Biological, Geological and Environmental Sciences (BiGeA), University of Bologna, Via Selmi, 3, 40126 Bologna BO, Italy
Interests: arthropoda; genomics; phylogenetic analysis; genetic diversity; molecular ecology; molecular evolution; molecular phylogenetics; phylogeography; DNA barcoding; hybridization; molecular taxonomy; nucleic acids; transposable elements; retrotransposons; zoology
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 non-coding regions, makes transposable elements particularly important for genome functionality and evolution. After their first discovery nearly 70 years ago, transposable elements were 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 ageing.

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 sequence information available. Therefore, we are now 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, by selecting 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.

Prof. Dr. Teresa Capriglione
Dr. Andrea Luchetti
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 (13 papers)

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20 pages, 2216 KiB

Open AccessArticle

Long Tandem Arrays of Cassandra Retroelements and Their Role in Genome Dynamics in Plants

by Ruslan Kalendar, Olga Raskina, Alexander Belyayev and Alan H. Schulman

Int. J. Mol. Sci. 2020, 21(8), 2931; https://doi.org/10.3390/ijms21082931 - 22 Apr 2020

Cited by 27 | Viewed by 4526

Abstract

Retrotransposable elements are widely distributed and diverse in eukaryotes. Their copy number increases through reverse-transcription-mediated propagation, while they can be lost through recombinational processes, generating genomic rearrangements. We previously identified extensive structurally uniform retrotransposon groups in which no member contains the gag, pol, or env internal domains. Because of the lack of protein-coding capacity, these groups are non-autonomous in replication, even if transcriptionally active. The Cassandra element belongs to the non-autonomous group called terminal-repeat retrotransposons in miniature (TRIM). It carries 5S RNA sequences with conserved RNA polymerase (pol) III promoters and terminators in its long terminal repeats (LTRs). Here, we identified multiple extended tandem arrays of Cassandra retrotransposons within different plant species, including ferns. At least 12 copies of repeated LTRs (as the tandem unit) and internal domain (as a spacer), giving a pattern that resembles the cellular 5S rRNA genes, were identified. A cytogenetic analysis revealed the specific chromosomal pattern of the Cassandra retrotransposon with prominent clustering at and around 5S rDNA loci. The secondary structure of the Cassandra retroelement RNA is predicted to form super-loops, in which the two LTRs are complementary to each other and can initiate local recombination, leading to the tandem arrays of Cassandra elements. The array structures are conserved for Cassandra retroelements of different species. We speculate that recombination events similar to those of 5S rRNA genes may explain the wide variation in Cassandra copy number. Likewise, the organization of 5S rRNA gene sequences is very variable in flowering plants; part of what is taken for 5S gene copy variation may be variation in Cassandra number. The role of the Cassandra 5S sequences remains to be established. Full article

(This article belongs to the Special Issue Transposable Elements)

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15 pages, 14867 KiB

Open AccessArticle

Riding the Wave: The SINE-Specific V Highly-Conserved Domain Spread into Mammalian Genomes Exploiting the Replication Burst of the MER6 DNA Transposon

by Andrea Luchetti, Mariana Lomiento and Barbara Mantovani

Int. J. Mol. Sci. 2019, 20(22), 5607; https://doi.org/10.3390/ijms20225607 - 9 Nov 2019

Cited by 1 | Viewed by 3667

Abstract

Transposable elements are widely distributed within genomes where they may significantly impact their evolution and cell functions. Short interspersed elements (SINEs) are non-autonomous, fast-evolving elements, but some of them carry a highly conserved domain (HCD), whose sequence remained substantially unchanged throughout the metazoan evolution. SINEs carrying the HCD called V are absent in amniote genomes, but V-like sequences were found within the miniature inverted-repeat transposable element (MITE) MER6 in Homo sapiens. In the present work, the genomic distribution and evolution of MER6 are investigated, in order to reconstruct the origin of human V domain and to envisage its possible functional role. The analysis of 85 tetrapod genomes revealed that MER6 and its variant MER6A are found in primates, while only the MER6A variant was found in bats and eulipotyphlans. These MITEs appeared no longer active, in line with literature data on mammalian DNA transposons. Moreover, they appeared to have originated from a Mariner element found in turtles and from a V-SINE from bony fishes. MER6 insertions were found within genes and conserved in mRNAs: in line with previous hypothesis on functional role of HCDs, the MER6 V domain may be important for cell function also in mammals. Full article

(This article belongs to the Special Issue Transposable Elements)

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11 pages, 1017 KiB

Open AccessArticle

Expression of A New Endogenous Retrovirus-Associated Transcript in Hodgkin Lymphoma Cells

by Jana Schneider, Ines Volkmer, Kristina Engel, Alexander Emmer and Martin S. Staege

Int. J. Mol. Sci. 2019, 20(21), 5320; https://doi.org/10.3390/ijms20215320 - 25 Oct 2019

Cited by 3 | Viewed by 2738

Abstract

During characterization of a cDNA library from the Hodgkin lymphoma (HL) cell line L-1236, we discovered a new transcript derived from chromosome 1 at the long intergenic non-protein coding RNA 1768 (LINC01768)/colony stimulating factor 1 (CSF1) region. The first exon of this transcript from Hodgkin lymphoma cells (THOLE) starts in the predicted exon 4 of LINC01768 and is part of an endogenous retrovirus (ERV) from the HUERS-P1/LTR8 family. High expression of THOLE was only detectable in HL cell line L-1236. The expression of THOLE in L-1236 cell is another example for ERV/LTR-associated gene expression in HL cells. At the genome level, the HUERS-P1/LTR8 region including THOLE is only present in Hominoidea. The influence of ERV/LTRs on gene expression might explain the characteristic phenotype of human HL. Full article

(This article belongs to the Special Issue Transposable Elements)

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17 pages, 3382 KiB

Open AccessArticle

Alu RNA Modulates the Expression of Cell Cycle Genes in Human Fibroblasts

by Simona Cantarella, Davide Carnevali, Marco Morselli, Anastasia Conti, Matteo Pellegrini, Barbara Montanini and Giorgio Dieci

Int. J. Mol. Sci. 2019, 20(13), 3315; https://doi.org/10.3390/ijms20133315 - 5 Jul 2019

Cited by 13 | Viewed by 5372

Abstract

Alu retroelements, whose retrotransposition requires prior transcription by RNA polymerase III to generate Alu RNAs, represent the most numerous non-coding RNA (ncRNA) gene family in the human genome. Alu transcription is generally kept to extremely low levels by tight epigenetic silencing, but it has been reported to increase under different types of cell perturbation, such as viral infection and cancer. Alu RNAs, being able to act as gene expression modulators, may be directly involved in the mechanisms determining cellular behavior in such perturbed states. To directly address the regulatory potential of Alu RNAs, we generated IMR90 fibroblasts and HeLa cell lines stably overexpressing two slightly different Alu RNAs, and analyzed genome-wide the expression changes of protein-coding genes through RNA-sequencing. Among the genes that were upregulated or downregulated in response to Alu overexpression in IMR90, but not in HeLa cells, we found a highly significant enrichment of pathways involved in cell cycle progression and mitotic entry. Accordingly, Alu overexpression was found to promote transition from G1 to S phase, as revealed by flow cytometry. Therefore, increased Alu RNA may contribute to sustained cell proliferation, which is an important factor of cancer development and progression. Full article

(This article belongs to the Special Issue Transposable Elements)

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9 pages, 1416 KiB

Open AccessCommunication

Identification of a Retroelement-Containing Human Transcript Induced in the Nucleus by Vaccination

by Tomoyuki Honda, Keiko Takemoto and Keiji Ueda

Int. J. Mol. Sci. 2019, 20(12), 2875; https://doi.org/10.3390/ijms20122875 - 13 Jun 2019

Cited by 5 | Viewed by 3064

Abstract

Endogenous retroelements constitute almost half of the mammalian genome. Given that more than 60% of human genomic bases are transcribed, transcripts containing these retroelements may impact various biological processes. However, the physiological roles of most retroelement-containing transcripts are yet to be revealed. Here, we profiled the expression of retroelement-containing human transcripts during vaccination and found that vaccination upregulated transcripts containing only particular retroelements, such as the MLT-int element of endogenous retroviruses. MLT-int-containing transcripts were distributed mainly in the nucleus, suggesting their unique roles in the nucleus. Furthermore, we demonstrated that MLT-int RNA suppressed interferon promoter activity in the absence of immune stimuli. Based on these lines of evidence, we speculate a model of a role of the previously unnoticed MLT-int element in preventing excess innate immune activation after elimination of immune stimuli. Our results may emphasize the importance of retroelement-containing transcripts in maintaining host immune homeostasis. Full article

(This article belongs to the Special Issue Transposable Elements)

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17 pages, 2635 KiB

Open AccessArticle

miR-128 Restriction of LINE-1 (L1) Retrotransposition Is Dependent on Targeting hnRNPA1 mRNA

by Lianna Fung, Herlinda Guzman, Evgueni Sevrioukov, Adam Idica, Eddie Park, Aurore Bochnakian, Iben Daugaard, Douglas Jury, Ali Mortazavi, Dimitrios G. Zisoulis and Irene M. Pedersen

Int. J. Mol. Sci. 2019, 20(8), 1955; https://doi.org/10.3390/ijms20081955 - 21 Apr 2019

Cited by 14 | Viewed by 4509

Abstract

The majority of the human genome is made of transposable elements, giving rise to interspaced repeats, including Long INterspersed Element-1s (LINE-1s or L1s). L1s are active human transposable elements involved in genomic diversity and evolution; however, they can also contribute to genomic instability and diseases. L1s require host factors to complete their life cycles, whereas the host has evolved numerous mechanisms to restrict L1-induced mutagenesis. Restriction mechanisms in somatic cells include methylation of the L1 promoter, anti-viral factors and RNA-mediated processes such as small RNAs. microRNAs (miRNAs or miRs) are small non-coding RNAs that post-transcriptionally repress multiple target genes often found in the same cellular pathways. We have recently established that miR-128 functions as a novel restriction factor inhibiting L1 mobilization in somatic cells. We have further demonstrated that miR-128 functions through a dual mechanism; by directly targeting L1 RNA for degradation and indirectly by inhibiting a cellular co-factor which L1 is dependent on to transpose to new genomic locations (TNPO1). Here, we add another piece to the puzzle of the enigmatic L1 lifecycle. We show that miR-128 also inhibits another key cellular factor, hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1), by significantly reducing mRNA and protein levels through direct interaction with the coding sequence (CDS) of hnRNPA1 mRNA. In addition, we demonstrate that repression of hnRNPA1 using hnRNPA1-shRNA significantly decreases de novo L1 retro-transposition and that induced hnRNPA1 expression enhances L1 mobilization. Furthermore, we establish that hnRNPA1 is a functional target of miR-128. Finally, we determine that induced hnRNPA1 expression in miR-128-overexpressing cells can partly rescue the miR-128-induced repression of L1′s ability to transpose to different genomic locations. Thus, we have identified an additional mechanism by which miR-128 represses L1 retro-transposition and mediates genomic stability. Full article

(This article belongs to the Special Issue Transposable Elements)

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19 pages, 2872 KiB

Open AccessArticle

Insertion Hot Spots of DIRS1 Retrotransposon and Chromosomal Diversifications among the Antarctic Teleosts Nototheniidae

by Juliette Auvinet, Paula Graça, Laura Ghigliotti, Eva Pisano, Agnès Dettaï, Catherine Ozouf-Costaz and Dominique Higuet

Int. J. Mol. Sci. 2019, 20(3), 701; https://doi.org/10.3390/ijms20030701 - 6 Feb 2019

Cited by 9 | Viewed by 3575

Abstract

By their faculty to transpose, transposable elements are known to play a key role in eukaryote genomes, impacting both their structuration and remodeling. Their integration in targeted sites may lead to recombination mechanisms involved in chromosomal rearrangements. The Antarctic fish family Nototheniidae went through several waves of species radiations. It is a suitable model to study transposable element (TE)-mediated mechanisms associated to genome and chromosomal diversifications. After the characterization of Gypsy (GyNoto), Copia (CoNoto), and DIRS1 (YNoto) retrotransposons in the genomes of Nototheniidae (diversity, distribution, conservation), we focused on their chromosome location with an emphasis on the three identified nototheniid radiations (the Trematomus, the plunderfishes, and the icefishes). The strong intrafamily TE conservation and wide distribution across species of the whole family suggest an ancestral acquisition with potential secondary losses in some lineages. GyNoto and CoNoto (including Hydra and GalEa clades) mostly produced interspersed signals along chromosomal arms. On the contrary, insertion hot spots accumulating in localized regions (mainly next to centromeric and pericentromeric regions) highlighted the potential role of YNoto in chromosomal diversifications as facilitator of the fusions which occurred in many nototheniid lineages, but not of the fissions. Full article

(This article belongs to the Special Issue Transposable Elements)

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9 pages, 1428 KiB

Open AccessArticle

Inhibition of LINE-1 Retrotransposition by Capsaicin

by Yuki Nishikawa, Ryota Nakayama, Shunsuke Obika, Eriko Ohsaki, Keiji Ueda and Tomoyuki Honda

Int. J. Mol. Sci. 2018, 19(10), 3243; https://doi.org/10.3390/ijms19103243 - 19 Oct 2018

Cited by 19 | Viewed by 5175

Abstract

Long interspersed nuclear element 1 (LINE-1 or L1) is a non-long terminal repeat (LTR) retrotransposon that constitutes approximately 17% of the human genome. Since approximately 100 copies are still competent for retrotransposition to other genomic loci, dysregulated retrotransposition of L1 is considered to be a major risk factor of endogenous mutagenesis in humans. Thus, it is important to find drugs to regulate this process. Although various chemicals are reportedly capable of affecting L1 retrotransposition, it is poorly understood whether phytochemicals modulate L1 retrotransposition. Here, we screened a library of compounds that were derived from phytochemicals for reverse transcriptase (RT) inhibition with an in vitro RT assay. We identified capsaicin as a novel RT inhibitor that also suppressed L1 retrotransposition. The inhibitory effect of capsaicin on L1 retrotransposition was mediated neither through its receptor, nor through its modulation of the L1 promoter and/or antisense promoter activity, excluding the possibility that capsaicin indirectly affected L1 retrotransposition. Collectively, capsaicin suppressed L1 retrotransposition most likely by inhibiting the RT activity of L1 ORF2p, which is the L1-encoded RT responsible for L1 retrotransposition. Given that L1-mediated mutagenesis can cause tumorigenesis, our findings suggest the potential of capsaicin for suppressing cancer development. Full article

(This article belongs to the Special Issue Transposable Elements)

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10 pages, 2033 KiB

Open AccessArticle

Exploring the Remote Ties between Helitron Transposases and Other Rolling-Circle Replication Proteins

by Pedro Heringer and Gustavo C. S. Kuhn

Int. J. Mol. Sci. 2018, 19(10), 3079; https://doi.org/10.3390/ijms19103079 - 9 Oct 2018

Cited by 8 | Viewed by 3690

Abstract

Rolling-circle replication (RCR) elements constitute a diverse group that includes viruses, plasmids, and transposons, present in hosts from all domains of life. Eukaryotic RCR transposons, also known as Helitrons, are found in species from all eukaryotic kingdoms, sometimes representing a large portion of their genomes. Despite the impact of Helitrons on their hosts, knowledge about their relationship with other RCR elements is still elusive. Here, we compared the endonuclease domain sequence of Helitron transposases with the corresponding region from RCR proteins found in a wide variety of mobile genetic elements. To do that, we used a stepwise alignment approach followed by phylogenetic and multidimensional scaling analyses. Although it has been suggested that Helitrons might have originated from prokaryotic transposons or eukaryotic viruses, our results indicate that Helitron transposases share more similarities with proteins from prokaryotic viruses and plasmids instead. We also provide evidence for the division of RCR endonucleases into three groups (Y1, Y2, and Yx), covering the whole diversity of this protein family. Together, these results point to prokaryotic elements as the likely closest ancestors of eukaryotic RCR transposons, and further demonstrate the fluidity that characterizes the boundaries separating viruses, plasmids, and transposons. Full article

(This article belongs to the Special Issue Transposable Elements)

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Review

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27 pages, 1753 KiB

Open AccessReview

Endogenous Retroviruses Activity as a Molecular Signature of Neurodevelopmental Disorders

by Emanuela Balestrieri, Claudia Matteucci, Chiara Cipriani, Sandro Grelli, Laura Ricceri, Gemma Calamandrei and Paola Sinibaldi Vallebona

Int. J. Mol. Sci. 2019, 20(23), 6050; https://doi.org/10.3390/ijms20236050 - 30 Nov 2019

Cited by 18 | Viewed by 5278

Abstract

Human endogenous retroviruses (HERVs) are genetic elements resulting from relics of ancestral infection of germline cells, now recognized as cofactors in the etiology of several complex diseases. Here we present a review of findings supporting the role of the abnormal HERVs activity in neurodevelopmental disorders. The derailment of brain development underlies numerous neuropsychiatric conditions, likely starting during prenatal life and carrying on during subsequent maturation of the brain. Autism spectrum disorders, attention deficit hyperactivity disorders, and schizophrenia are neurodevelopmental disorders that arise clinically during early childhood or adolescence, currently attributed to the interplay among genetic vulnerability, environmental risk factors, and maternal immune activation. The role of HERVs in human embryogenesis, their intrinsic responsiveness to external stimuli, and the interaction with the immune system support the involvement of HERVs in the derailed neurodevelopmental process. Although definitive proofs that HERVs are involved in neurobehavioral alterations are still lacking, both preclinical models and human studies indicate that the abnormal expression of ERVs could represent a neurodevelopmental disorders-associated biological trait in affected individuals and their parents. Full article

(This article belongs to the Special Issue Transposable Elements)

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11 pages, 623 KiB

Open AccessReview

Roles of Transposable Elements in the Different Layers of Gene Expression Regulation

by Denise Drongitis, Francesco Aniello, Laura Fucci and Aldo Donizetti

Int. J. Mol. Sci. 2019, 20(22), 5755; https://doi.org/10.3390/ijms20225755 - 15 Nov 2019

Cited by 33 | Viewed by 7029

Abstract

The biology of transposable elements (TEs) is a fascinating and complex field of investigation. TEs represent a substantial fraction of many eukaryotic genomes and can influence many aspects of DNA function that range from the evolution of genetic information to duplication, stability, and gene expression. Their ability to move inside the genome has been largely recognized as a double-edged sword, as both useful and deleterious effects can result. A fundamental role has been played by the evolution of the molecular processes needed to properly control the expression of TEs. Today, we are far removed from the original reductive vision of TEs as “junk DNA”, and are more convinced that TEs represent an essential element in the regulation of gene expression. In this review, we summarize some of the more recent findings, mainly in the animal kingdom, concerning the active roles that TEs play at every level of gene expression regulation, including chromatin modification, splicing, and protein translation. Full article

(This article belongs to the Special Issue Transposable Elements)

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14 pages, 1076 KiB

Open AccessReview

Transposable Elements Adaptive Role in Genome Plasticity, Pathogenicity and Evolution in Fungal Phytopathogens

by Nurhani Mat Razali, Boon Huat Cheah and Kalaivani Nadarajah

Int. J. Mol. Sci. 2019, 20(14), 3597; https://doi.org/10.3390/ijms20143597 - 23 Jul 2019

Cited by 43 | Viewed by 9486

Abstract

Transposable elements (TEs) are agents of genetic variability in phytopathogens as they are a source of adaptive evolution through genome diversification. Although many studies have uncovered information on TEs, the exact mechanism behind TE-induced changes within the genome remains poorly understood. Furthermore, convergent trends towards bigger genomes, emergence of novel genes and gain or loss of genes implicate a TE-regulated genome plasticity of fungal phytopathogens. TEs are able to alter gene expression by revamping the cis-regulatory elements or recruiting epigenetic control. Recent findings show that TEs recruit epigenetic control on the expression of effector genes as part of the coordinated infection strategy. In addition to genome plasticity and diversity, fungal pathogenicity is an area of economic concern. A survey of TE distribution suggests that their proximity to pathogenicity genes TEs may act as sites for emergence of novel pathogenicity factors via nucleotide changes and expansion or reduction of the gene family. Through a systematic survey of literature, we were able to conclude that the role of TEs in fungi is wide: ranging from genome plasticity, pathogenicity to adaptive behavior in evolution. This review also identifies the gaps in knowledge that requires further elucidation for a better understanding of TEs’ contribution to genome architecture and versatility. Full article

(This article belongs to the Special Issue Transposable Elements)

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15 pages, 967 KiB

Open AccessReview

Rex Retroelements and Teleost Genomes: An Overview

by Federica Carducci, Marco Barucca, Adriana Canapa and Maria Assunta Biscotti

Int. J. Mol. Sci. 2018, 19(11), 3653; https://doi.org/10.3390/ijms19113653 - 20 Nov 2018

Cited by 21 | Viewed by 4244

Abstract

Repetitive DNA is an intriguing portion of the genome still not completely discovered and shows a high variability in terms of sequence, genomic organization, and evolutionary mode. On the basis of the genomic organization, it includes satellite DNAs, which are organized as long arrays of head-to-tail linked repeats, and transposable elements, which are dispersed throughout the genome. These repeated elements represent a considerable fraction of vertebrate genomes contributing significantly in species evolution. In this review, we focus our attention on Rex1, Rex3 and Rex6, three elements specific of teleost genomes. We report an overview of data available on these retroelements highlighting their significative impact in chromatin and heterochromatin organization, in the differentiation of sex chromosomes, in the formation of supernumerary chromosomes, and in karyotype evolution in teleosts. Full article

(This article belongs to the Special Issue Transposable Elements)

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