An RNA splicing system that excises DNA transposons from animal mRNAs

<p indent="0mm">Transposable elements (TEs) are mobile DNA sequences within the genome, and their structure and transposition mechanism are highly diverse. TEs can be divided into retrotransposons (RTs; Class I) and DNA transposons (Class II), depending on whether their transposition intermediate is RNA or DNA. RTs transpose in a “copy-and-paste” manner and are therefore considered to be an essential contributor during genome expansion. RTs can be further divided into long terminal repeat retrotransposons (LTR-RTs) and non-long terminal repeat retrotransposons (non-LTR-RTs). <italic>Copia</italic> and <italic>Gypsy</italic> are two superfamilies of LTR-RTs commonly found in plant genomes, and their structural differences lie in the <italic>INT</italic> positions in the internal sequence of the <italic>pol</italic> open reading frame (ORF). Non-LTR-RTs include long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), which lack LTRs and usually have poly(A) or simple repeats at their 3′ end. DNA transposons directly cut the DNA sequence at the original site by transposase and insert a new site, similar to “cut-and-paste”. Insertion of DNA transposons into new sites results in target site duplications (TSDs), and DNA strand breaks due to transposition are repaired by DNA repair mechanisms. DNA transposons in plants can be further divided into “cut-and-paste” transposons and <italic>Helitrons</italic> with the “rolling circle” transposition pattern. TEs play an important role in genome evolution. In the process of their insertion, deletion, and amplification, the host may alter its genome size, gene expression, and gene function. Additionally, TEs may mediate chromosomal rearrangements through homologous recombination or alternative transposition. Overall, TEs are very powerful mutagens that can affect the stability of their host genomes. In order to defend against the transposition of TEs, the host has evolved various silencing mechanisms. In plants, the silencing of TEs is mainly established through RNA-directed DNA methylation (RdDM), which can stably repress the activity of TEs across generations. Methylation not only silences TEs but may also result in DNA methylation of nearby genes and affect expression and function of host genes. Interestingly, the phenotypic differences caused by the insertion of TEs play an important role in crop domestication. Methylation does not always keep TEs silent, such as burst events in some TE families. The evidence for the interaction between TEs and the host is growing, especially under environmental stress conditions, and TEs can be re-activated to help the host survive under stressful conditions. Furthermore, the insertion of TEs is preferred in many cases, and their insertion can be tolerated. Thus, TEs may not be completely inhibited, and they and their hosts may develop a cooperative relationship under environmental stress. This review summarizes some relevant research on TEs in plant genome evolution, introduces commonly occurring TEs found in plants, and examines how TEs are involved in plant genome evolution, epigenetic regulation, and the symbiotic relationship with the host under cooperative stress.

Eukaryotes contain numerous transposable or mobile elements capable of parasite-like proliferation in the host genome. All known transposable elements in eukaryotes belong to two types: retrotransposons and DNA transposons. Here we report a previously uncharacterized class of DNA transposons called Polintons that populate genomes of protists, fungi, and animals, including entamoeba, soybean rust, hydra, sea anemone, nematodes, fruit flies, beetle, sea urchin, sea squirt, fish, lizard, frog, and chicken. Polintons from all these species are characterized by a unique set of proteins necessary for their transposition, including a protein-primed DNA polymerase B, retroviral integrase, cysteine protease, and ATPase. In addition, Polintons are characterized by 6-bp target site duplications, terminal-inverted repeats that are several hundred nucleotides long, and 5'-AG and TC-3' termini. Analogously to known transposable elements, Polintons exist as autonomous and nonautonomous elements. Our data suggest that Polintons have evolved from a linear plasmid that acquired a retroviral integrase at least 1 billion years ago. According to the model of Polinton transposition proposed here, a Polinton DNA molecule excised from the genome serves as a template for extrachromosomal synthesis of its double-stranded DNA copy by the Polinton-encoded DNA polymerase and is inserted back into genome by its integrase.

Transposons or transposable elements (TEs) are ubiquitous and most abundant DNA components in higher eukaryotes. Recent sequencing of the Brassica rapa and B. oleracea genomes revealed that the amplification of TEs is one of the main factors inducing the difference in genome size. However, the expressions of TEs and the TE effects on gene regulation and functions of these two Brassica diploid species were unclear. Here, we analyzed the RNA sequencing data of leaves, roots, and stems from B. rapa and B. oleracea. Our data showed that overall TEs in either genome expressed at very low levels, and the expression levels of different TE categories and families varied among different organs. Moreover, even for the same TE category or family, the expression activities were distinct between the two Brassica diploids. Forty-one and nine LTR retrotransposons with the transcripts that read into their adjacent sequences have the distances shorter than 2 kb and 100 bp compared to the downstream genes. These LTR retrotransposon readout transcriptions may produce sense or antisense transcripts of nearby genes, with the effects on activating or silencing corresponding genes. Meanwhile, intact LTRs were detected at stronger readout activities than solo LTRs. Of the TEs inserted into genes, the frequencies were ob-served at a higher level in B. rapa than in B. oleracea. In addition, DNA transposons were prone to insert or retain in the intronic regions of genes in either Brassica genomes. These results revealed that the TEs may have potential effects on regulating protein coding genes.

A novel family of miniature inverted repeat transposable elements (MITEs) named Pony was discovered in the yellow fever mosquito, Aedes aegypti. It has all the characteristics of MITEs, including terminal inverted repeats, no coding potential, A+T richness, small size, and the potential to form stable secondary structures. Past mobility of PONY: was indicated by the identification of two Pony insertions which resulted in the duplication of the TA dinucleotide targets. Two highly divergent subfamilies, A and B, were identified in A. aegypti based on sequence comparison and phylogenetic analysis of 38 elements. These subfamilies showed less than 62% sequence similarity. However, within each subfamily, most elements were highly conserved, and multiple subgroups could be identified, indicating recent amplifications from different source genes. Different scenarios are presented to explain the evolutionary history of these subfamilies. Both subfamilies share conserved terminal inverted repeats similar to those of the Tc2 DNA transposons in Caenorhabditis elegans, indicating that Pony may have been borrowing the transposition machinery from a Tc2-like transposon in mosquitoes. In addition to the terminal inverted repeats, full-length and partial subterminal repeats of a sequence motif TTGATTCAWATTCCGRACA represent the majority of the conservation between the two subfamilies, indicating that they may be important structural and/or functional components of the Pony elements. In contrast to known autonomous DNA transposons, both subfamilies of PONY: are highly reiterated in the A. aegypti genome (8,400 and 9, 900 copies, respectively). Together, they constitute approximately 1. 1% of the entire genome. Pony elements were frequently found near other transposable elements or in the noncoding regions of genes. The relative abundance of MITEs varies in eukaryotic genomes, which may have in part contributed to the different organizations of the genomes and reflect different types of interactions between the hosts and these widespread transposable elements.

Transposable elements (TEs) are important drivers of genome evolution. Nonetheless, TE annotation remains a complex and challenging task. As more genomes from phylogenetically diverse species are published, a comprehensive pipeline for accurate annotation of diverse TEs is increasingly important. Recently, (Ou et al. Genome Biol. 20:275, 2019) developed a new comprehensive pipeline, Extensive De novo Transposable element Annotator (EDTA), and benchmarked its performance on the genomes of three species: maize, wheat, and fruit fly. Because TE landscapes can vary tremendously across species, we tested EDTA’s performance on four additional genomes with different TE landscapes: mouse, zebrafish, zebra finch, and chicken. Our analysis reveals that EDTA faces challenges with repeat classification in these genomes and underperforms overall relative to its benchmark dataset. Notably, EDTA consistently misclassifies nonLTR retrotransposons as DNA transposons, resulting in erroneous TE annotations for species with considerable repertoires of nonLTR retrotransposons. Overall, we set expectations for EDTA’s performance on genomes spanning additional diversity, urge caution when using EDTA on genomes with divergent TE repertoires from the species on which it was initially benchmarked, and hope to motivate the development of methods that are robust to both the diversity of TEs and TE landscapes observed across species.

The Colletotrichum genus comprises fungal pathogens that inflict severe diseases on a wide range of hosts, including economically important plants. Colletotrichum lindemuthianum is the causative agent of anthracnose in common beans (Phaseolus vulgaris), leading to significant production and quality losses in this essential legume crop. Transposable elements are mobile genetic units found across all life domains that play a significant role in genomic plasticity, which is particularly relevant for phytopathogenic fungi such as C. lindemuthianum. These elements are classified into two distinct classes based on their transposition mode: Class I transposons rely on an RNA intermediate to transpose, while Class II transposons transpose directly as DNA. Additionally, transposons can be divided as autonomous and non- autonomous elements, with the latter depending on other transposable elements for their mobility due to the absence of essential functional components. The Tc1/mariner is a widely distributed Class II transposon superfamily. Miniature- inverted repeat elements (MITEs) are non-autonomous elements derived from Class II elements like the Tc1/mariner family. Considering the crucial role of transposons in generating genetic variability, this study aimed to identify and characterize Tc1/mariner and MITE transposable elements within the genome of C. lindemuthianum, using an in-silico approach. A total of 615 sequences related to Tc1/mariner elements were identified, which represented 0.78% of the genome. Among them, 536 copies were considered degenerated due to nearly unrecognizable terminal inverted repeats. Only one family of complete elements was found, and a derived MITE family was identified. Both the parental and derived families displayed a strong tendency to be found inserted within gene promoter regions. Moreover, two other MITE families were characterized, but the elements that originated them could not be identified. The elements from both families were primarily located within transposon-enriched regions. All complete elements showed putative transposase ORFs interrupted with multiple stop codons, suggesting that there are no active Tc1/mariner elements in C. lindemuthianum. Our analysis revealed that these elements were heavily affected by repeat-induced point mutations (RIP). Furthermore, we identified copies of both methyltransferases involved in RIP, which further supports that this mechanism or a RIP-like mechanism is active in C. lindemuthianum. The insights gained from this study contribute to a better understanding of the Tc1/mariner and MITE landscape as well as defense mechanisms against transposon proliferation of C. lindemuthianum, providing a foundation for further investigations into the genetic variability and transposable element exaptation of this economically important plant pathogen. Keywords: Class II transposons. Non-autonomous transposons. Repetitive DNA. Genome defense.

Characterization of three DNA transposons in the Dutch elm disease fungi and evidence of repeat-induced point (RIP) mutations

Transposable elements (TEs) comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers.

Comparative genomics has revealed that major vertebrate lineages contain quantitatively and qualitatively different populations of retrotransposable elements and DNA transposons, with important differences also frequently observed between species of the same lineage. This is essentially due to (i) the differential evolution of ancestral families of transposable elements, with evolutionary scenarios ranging from complete extinction to massive invasion; (ii) the lineage-specific introduction of transposable elements by infection and horizontal transfer, as exemplified by endogenous retroviruses; and (iii) the lineage-specific emergence of new transposable elements, as particularly observed for non-coding retroelements called short interspersed elements (SINEs). During vertebrate evolution, transposable elements have repeatedly contributed regulatory and coding sequences to the host, leading to the emergence of new lineage-specific gene regulations and functions. In all vertebrate lineages, there is evidence of transposable element-mediated genomic rearrangements such as insertions, deletions, inversions and duplications potentially associated with or subsequent to speciation events. Taken together, these observations indicate that transposable elements are major drivers of genomic and biological diversity in vertebrates, with possible important roles in speciation and major evolutionary transitions.

Transposable elements encoding functional proteins: pitfalls in unprocessed genomic data?

Transposable elements (TEs) have been implicated in the generation of genetic rearrangements, but their potential to mediate changes in the organization and architecture of host genomes could be even greater than previously thought. Here, we describe the naturally occurring structural and nucleotide variation around two TE insertions in the genome of Drosophila buzzatii. The studied regions correspond to the breakpoints of a widespread chromosomal inversion generated by ectopic recombination between oppositely oriented copies of a TE named Galileo. A detailed molecular analysis by Southern hybridization, PCR amplification, and DNA sequencing of 7.1 kb surrounding the inversion breakpoints in 39 D. buzzatii lines revealed an unprecedented degree of restructuring, consisting of 22 insertions of ten previously undescribed TEs, 13 deletions, 1 duplication, and 1 small inversion. All of these alterations occurred exclusively in inverted chromosomes and appear to have accumulated after the insertion of the Galileo elements, within or close to them. The nucleotide variation at the studied regions is six times lower in inverted than in noninverted chromosomes, suggesting that most of the observed changes originated in only 84,000 years. Galileo elements thus seemed to promote the transformation of these, otherwise normal, chromosomal regions in genetically unstable hotspots and highly efficient traps for transposon insertions. The particular features of two new Galileo copies found indicate that this TE belongs to the Foldback family. Together, our results strengthen the importance of TEs, and especially DNA transposons, as inducers of genome plasticity in evolution.

Sex chromosome differentiation is subject to independent evolutionary processes among different lineages. The accumulation of repetitive DNAs and consequent crossing-over restriction guide the origin of the heteromorphic sex chromosome region. Several Neotropical fish species have emerged as interesting models for understanding evolution and genome diversity, although knowledge of their genomes is scarce. Here, we investigate the content of repetitive DNAs between males and females of Apareiodon sp. based on large-scale genomic data focusing on W sex chromosome differentiation. In Apareiodon, females are the heterogametic sex (ZW) and males are the homogametic sex (ZZ). The genome size estimate for Apareiodon was 1.2Gb (with ~ 42× and ~ 47× coverage for males and females, respectively). In Apareiodon sp., approximately 36% of the genome was composed of repetitive DNAs and transposable elements (TEs) were the most abundant class. Read coverage analysis revealed different amounts of repetitive DNAs in males and females. The female-enriched clusters were located on the W sex chromosome and were mostly composed of microsatellite expansions and DNA transposons. Landscape analysis of TE contents demonstrated two major waves of invasions of TEs in the Apareiodon genome. Estimation of TE insertion times correlated with in situ locations permitted the inference that helitron, Tc1-mariner, and CMC EnSpm DNA transposons accumulated repeated copies during W chromosome differentiation between 20 and 12 million years ago. DNA transposons and microsatellite expansions appeared to be major players in W chromosome differentiation and to guide modifications in the genome content of the heteromorphic sex chromosomes.

Transposable elements (TEs), the movement of which can damage the genome, are epigenetically silenced in eukaryotes. Intriguingly, TEs are activated in the sperm companion cell - vegetative cell (VC) - of the flowering plant Arabidopsis thaliana. However, the extent and mechanism of this activation are unknown. Here we show that about 100 heterochromatic TEs are activated in VCs, mostly by DEMETER-catalyzed DNA demethylation. We further demonstrate that DEMETER access to some of these TEs is permitted by the natural depletion of linker histone H1 in VCs. Ectopically expressed H1 suppresses TEs in VCs by reducing DNA demethylation and via a methylation-independent mechanism. We demonstrate that H1 is required for heterochromatin condensation in plant cells and show that H1 overexpression creates heterochromatic foci in the VC progenitor cell. Taken together, our results demonstrate that the natural depletion of H1 during male gametogenesis facilitates DEMETER-directed DNA demethylation, heterochromatin relaxation, and TE activation.

Transposable elements (TEs), the movement of which can damage the genome, are epigenetically silenced in eukaryotes. Intriguingly, TEs are activated in the sperm companion cell – vegetative cell (VC) – of the flowering plant Arabidopsis thaliana. However, the extent and mechanism of this activation are unknown. Here we show that about 100 heterochromatic TEs are activated in VCs, mostly by DEMETER-catalyzed DNA demethylation. We further demonstrate that DEMETER access to some of these TEs is permitted by the natural depletion of linker histone H1 in VCs. Ectopically expressed H1 suppresses TEs in VCs by reducing DNA demethylation and via a methylation-independent mechanism. We demonstrate that H1 is required for heterochromatin condensation in plant cells and show that H1 overexpression creates heterochromatic foci in the VC progenitor cell. Taken together, our results demonstrate that the natural depletion of H1 during male gametogenesis facilitates DEMETER-directed DNA demethylation, heterochromatin relaxation, and TE activation.

Infection of germline cells with retroviruses initiates permanent proviral colonization of the germline genome. The germline-integrated proviruses, called endogenous retroviruses (ERVs), are inherited to offspring in a Mendelian order and belong to the transposable element family. Endogenous retroviruses and other long terminal repeat retroelements constitute ~8% and ~10% of the human and mouse genomes, respectively. It is likely that each individual has a distinct genomic ERV profile. Recent studies have revealed that a substantial fraction of ERVs retains the coding potentials necessary for virion assembly and replication. There are several layers of potential mechanisms controlling ERV expression: intracellular transcription environment (e.g., transcription factor pool, splicing machinery, hormones), epigenetic status of the genome (e.g., proviral methylation, histone acetylation), profile of transcription regulatory elements on each ERV's promoter, and a range of stress signals (e.g., injury, infection, environment). Endogenous retroviruses may exert pathophysiologic effects by infection followed by random reintegration into the genome, by their gene products (e.g., envelope, superantigen), and by altering the expression of neighboring genes. Several studies have provided evidence that ERVs are associated with a range of pathogenic processes involving multiple sclerosis, systemic lupus erythematosus, breast cancer, and the response to burn injury. For instance, the proinflammatory properties of the human ERV-W envelope protein play a central role in demyelination of oligodendrocytes. As reviewed in this article, recent advances in ERV biology and mammalian genomics suggest that ERVs may have a profound influence on various pathogenic processes including the response to injury and infection. Understanding the roles of ERVs in the pathogenesis of injury and infection will broaden insights into the underlying mechanisms of systemic immune disorder and organ failure in these patients.