Regulation of Mobile Genetic Elements at the Molecular Level

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Genetics and Genomics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 18285

Special Issue Editor


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Guest Editor
GReD, Université Clermont Auvergne, CNRS, INSERM, Faculté de Médecine, 63000 Clermont-Ferrand, France
Interests: transposable elements; small RNA; piRNA; PIWI pathway; RNA biology; epigenetics; piRNA cluster; germline; regulation of gene expression

Special Issue Information

Dear Colleagues,

When Barbara McClintock discovered mobile genetic elements in the 1950s, did she suspect the magnitude, extent, and consequences of the mobility of these elements in the living world? Indeed, mobile genetic elements, also called transposable elements, were subsequently discovered both in prokaryotes and in eukaryotes where they constitute a large part of genomes, as 45% in human, 80% in maize. Mobile elements are a source of mutations: in Drosophila, more than 80% of phenotypic mutations observed are due to transposition events; in humans, de novo insertions of transposable elements have been implicated in mutations leading to disease, as haemophilia, cancer, muscular dystrophy. Due to their repeated nature, mobile elements dispersed in the genome are also at the origin of important chromosomal rearrangements.

Today, we know that mobile genetic elements can have devastating or, on the contrary, beneficial effects on genomes. They can create disorders but they also play an essential role in the fluidity of genomes and in evolution. It is therefore extremely important to elucidate the regulatory mechanisms controlling mobile genetic elements in all their aspects at the molecular level, in the animal kingdom, in plants as in prokaryotes.

A number of different regulatory systems exist and operate in different organisms and in different tissues. In the metazoans germline, small RNAs interacting with PIWI family proteins (piRNAs) and small interfering RNAs (siRNAs) are key components of the pathways controlling transposable elements. Chromatin remodeling leads to transcriptional silencing of mobile elements. Truncated proteins derived from transposable elements themselves can control mobility as in the case of P elements in Drosophila. Somatic silencing mechanisms may be totally different from germline mechanisms in the same organism. Bringing together different areas of research in this Special Issue will help to expand our knowledge of the molecular mechanisms controlling mobile genetic elements in all their diversity.

Dr. Silke Jensen
Guest Editor

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Keywords

  • mobile genetic elements
  • transposable elements
  • post-transcriptional silencing
  • transcriptional silencing
  • small RNA
  • chromatin structure
  • epigenetics
  • genome plasticity

Published Papers (6 papers)

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Research

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16 pages, 1981 KiB  
Article
Paramutation-like Epigenetic Conversion by piRNA at the Telomere of Drosophila virilis
by Ana P. Dorador, Martina Dalikova, Stefan Cerbin, Chris M. Stillman, Molly G. Zych, R. Scott Hawley, Danny E. Miller, David A. Ray, Sergei Y. Funikov, Michael B. Evgen’ev and Justin P. Blumenstiel
Biology 2022, 11(10), 1480; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11101480 - 09 Oct 2022
Cited by 2 | Viewed by 2377
Abstract
First discovered in maize, paramutation is a phenomenon in which one allele can trigger an epigenetic conversion of an alternate allele. This conversion causes a genetically heterozygous individual to transmit alleles that are functionally the same, in apparent violation of Mendelian segregation. Studies [...] Read more.
First discovered in maize, paramutation is a phenomenon in which one allele can trigger an epigenetic conversion of an alternate allele. This conversion causes a genetically heterozygous individual to transmit alleles that are functionally the same, in apparent violation of Mendelian segregation. Studies over the past several decades have revealed a strong connection between mechanisms of genome defense against transposable elements by small RNA and the phenomenon of paramutation. For example, a system of paramutation in Drosophila melanogaster has been shown to be mediated by piRNAs, whose primary function is to silence transposable elements in the germline. In this paper, we characterize a second system of piRNA-mediated paramutation-like behavior at the telomere of Drosophila virilis. In Drosophila, telomeres are maintained by arrays of retrotransposons that are regulated by piRNAs. As a result, the telomere and sub-telomeric regions of the chromosome have unique regulatory and chromatin properties. Previous studies have shown that maternally deposited piRNAs derived from a sub-telomeric piRNA cluster can silence the sub-telomeric center divider gene of Drosophila virilis in trans. In this paper, we show that this silencing can also be maintained in the absence of the original silencing allele in a subsequent generation. The precise mechanism of this paramutation-like behavior may be explained by either the production of retrotransposon piRNAs that differ across strains or structural differences in the telomere. Altogether, these results show that the capacity for piRNAs to mediate paramutation in trans may depend on the local chromatin environment and proximity to the uniquely structured telomere regulated by piRNAs. This system promises to provide significant insights into the mechanisms of paramutation. Full article
(This article belongs to the Special Issue Regulation of Mobile Genetic Elements at the Molecular Level)
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14 pages, 3646 KiB  
Article
Meta-Analysis Suggests That Intron Retention Can Affect Quantification of Transposable Elements from RNA-Seq Data
by Nicolò Gualandi, Cristian Iperi, Mauro Esposito, Federico Ansaloni, Stefano Gustincich and Remo Sanges
Biology 2022, 11(6), 826; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11060826 - 27 May 2022
Cited by 7 | Viewed by 2798
Abstract
Transposable elements (TEs), also known as “jumping genes”, are repetitive sequences with the capability of changing their location within the genome. They are key players in many different biological processes in health and disease. Therefore, a reliable quantification of their expression as transcriptional [...] Read more.
Transposable elements (TEs), also known as “jumping genes”, are repetitive sequences with the capability of changing their location within the genome. They are key players in many different biological processes in health and disease. Therefore, a reliable quantification of their expression as transcriptional units is crucial to distinguish between their independent expression and the transcription of their sequences as part of canonical transcripts. TEs quantification faces difficulties of different types, the most important one being low reads mappability due to their repetitive nature preventing an unambiguous mapping of reads originating from their sequences. A large fraction of TEs fragments localizes within introns, which led to the hypothesis that intron retention (IR) can be an additional source of bias, potentially affecting accurate TEs quantification. IR occurs when introns, normally removed from the mature transcript by the splicing machinery, are maintained in mature transcripts. IR is a widespread mechanism affecting many different genes with cell type-specific patterns. We hypothesized that, in an RNA-seq experiment, reads derived from retained introns can introduce a bias in the detection of overlapping, independent TEs RNA expression. In this study we performed meta-analysis using public RNA-seq data from lymphoblastoid cell lines and show that IR can impact TEs quantification using established tools with default parameters. Reads mapped on intronic TEs were indeed associated to the expression of TEs and influence their correct quantification as independent transcriptional units. We confirmed these results using additional independent datasets, demonstrating that this bias does not appear in samples where IR is not present and that differential TEs expression does not impact on IR quantification. We concluded that IR causes the over-quantification of intronic TEs and differential IR might be confused with differential TEs expression. Our results should be taken into account for a correct quantification of TEs expression from RNA-seq data, especially in samples in which IR is abundant. Full article
(This article belongs to the Special Issue Regulation of Mobile Genetic Elements at the Molecular Level)
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13 pages, 2565 KiB  
Article
Quadruplex-Forming Motif Inserted into 3′UTR of Ty1his3-AI Retrotransposon Inhibits Retrotransposition in Yeast
by Viktor Tokan, Jose Luis Rodriguez Lorenzo, Pavel Jedlicka, Iva Kejnovska, Roman Hobza and Eduard Kejnovsky
Biology 2021, 10(4), 347; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10040347 - 20 Apr 2021
Cited by 1 | Viewed by 2371
Abstract
Guanine quadruplexes (G4s) serve as regulators of replication, recombination and gene expression. G4 motifs have been recently identified in LTR retrotransposons, but their role in the retrotransposon life-cycle is yet to be understood. Therefore, we inserted G4s into the 3′UTR of Ty1his3-AI retrotransposon [...] Read more.
Guanine quadruplexes (G4s) serve as regulators of replication, recombination and gene expression. G4 motifs have been recently identified in LTR retrotransposons, but their role in the retrotransposon life-cycle is yet to be understood. Therefore, we inserted G4s into the 3′UTR of Ty1his3-AI retrotransposon and measured the frequency of retrotransposition in yeast strains BY4741, Y00509 (without Pif1 helicase) and with G4-stabilization by N-methyl mesoporphyrin IX (NMM) treatment. We evaluated the impact of G4s on mRNA levels by RT-qPCR and products of reverse transcription by Southern blot analysis. We found that the presence of G4 inhibited Ty1his3-AI retrotransposition. The effect was stronger when G4s were on a transcription template strand which leads to reverse transcription interruption. Both NMM and Pif1p deficiency reduced the retrotransposition irrespective of the presence of a G4 motif in the Ty1his3-AI element. Quantity of mRNA and products of reverse transcription did not fully explain the impact of G4s on Ty1his3-AI retrotransposition indicating that G4s probably affect some other steps of the retrotransposon life-cycle (e.g., translation, VLP formation, integration). Our results suggest that G4 DNA conformation can tune the activity of mobile genetic elements that in turn contribute to shaping the eukaryotic genomes. Full article
(This article belongs to the Special Issue Regulation of Mobile Genetic Elements at the Molecular Level)
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Review

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20 pages, 2532 KiB  
Review
The Intricate Evolutionary Balance between Transposable Elements and Their Host: Who Will Kick at Goal and Convert the Next Try?
by Marianne Yoth, Silke Jensen and Emilie Brasset
Biology 2022, 11(5), 710; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11050710 - 06 May 2022
Cited by 1 | Viewed by 2655
Abstract
Transposable elements (TEs) are mobile DNA sequences that can jump from one genomic locus to another and that have colonized the genomes of all living organisms. TE mobilization and accumulation are an important source of genomic innovations that greatly contribute to the host [...] Read more.
Transposable elements (TEs) are mobile DNA sequences that can jump from one genomic locus to another and that have colonized the genomes of all living organisms. TE mobilization and accumulation are an important source of genomic innovations that greatly contribute to the host species evolution. To ensure their maintenance and amplification, TE transposition must occur in the germ cell genome. As TE transposition is also a major threat to genome integrity, the outcome of TE mobility in germ cell genomes could be highly dangerous because such mutations are inheritable. Thus, organisms have developed specialized strategies to protect the genome integrity from TE transposition, particularly in germ cells. Such effective TE silencing, together with ongoing mutations and negative selection, should result in the complete elimination of functional TEs from genomes. However, TEs have developed efficient strategies for their maintenance and spreading in populations, particularly by using horizontal transfer to invade the genome of novel species. Here, we discuss how TEs manage to bypass the host’s silencing machineries to propagate in its genome and how hosts engage in a fightback against TE invasion and propagation. This shows how TEs and their hosts have been evolving together to achieve a fine balance between transposition and repression. Full article
(This article belongs to the Special Issue Regulation of Mobile Genetic Elements at the Molecular Level)
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18 pages, 1377 KiB  
Review
Specificities and Dynamics of Transposable Elements in Land Plants
by Corinne Mhiri, Filipe Borges and Marie-Angèle Grandbastien
Biology 2022, 11(4), 488; https://0-doi-org.brum.beds.ac.uk/10.3390/biology11040488 - 23 Mar 2022
Cited by 18 | Viewed by 3446
Abstract
Transposable elements (TEs) are important components of most plant genomes. These mobile repetitive sequences are highly diverse in terms of abundance, structure, transposition mechanisms, activity and insertion specificities across plant species. This review will survey the different mechanisms that may explain the variability [...] Read more.
Transposable elements (TEs) are important components of most plant genomes. These mobile repetitive sequences are highly diverse in terms of abundance, structure, transposition mechanisms, activity and insertion specificities across plant species. This review will survey the different mechanisms that may explain the variability of TE patterns in land plants, highlighting the tight connection between TE dynamics and host genome specificities, and their co-evolution to face and adapt to a changing environment. We present the current TE classification in land plants, and describe the different levels of genetic and epigenetic controls originating from the plant, the TE itself, or external environmental factors. Such overlapping mechanisms of TE regulation might be responsible for the high diversity and dynamics of plant TEs observed in nature. Full article
(This article belongs to the Special Issue Regulation of Mobile Genetic Elements at the Molecular Level)
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22 pages, 449 KiB  
Review
Bioinformatics and Machine Learning Approaches to Understand the Regulation of Mobile Genetic Elements
by Ilektra-Chara Giassa and Panagiotis Alexiou
Biology 2021, 10(9), 896; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10090896 - 10 Sep 2021
Cited by 4 | Viewed by 3612
Abstract
Transposable elements (TEs, or mobile genetic elements, MGEs) are ubiquitous genetic elements that make up a substantial proportion of the genome of many species. The recent growing interest in understanding the evolution and function of TEs has revealed that TEs play a dual [...] Read more.
Transposable elements (TEs, or mobile genetic elements, MGEs) are ubiquitous genetic elements that make up a substantial proportion of the genome of many species. The recent growing interest in understanding the evolution and function of TEs has revealed that TEs play a dual role in genome evolution, development, disease, and drug resistance. Cells regulate TE expression against uncontrolled activity that can lead to developmental defects and disease, using multiple strategies, such as DNA chemical modification, small RNA (sRNA) silencing, chromatin modification, as well as sequence-specific repressors. Advancements in bioinformatics and machine learning approaches are increasingly contributing to the analysis of the regulation mechanisms. A plethora of tools and machine learning approaches have been developed for prediction, annotation, and expression profiling of sRNAs, for methylation analysis of TEs, as well as for genome-wide methylation analysis through bisulfite sequencing data. In this review, we provide a guided overview of the bioinformatic and machine learning state of the art of fields closely associated with TE regulation and function. Full article
(This article belongs to the Special Issue Regulation of Mobile Genetic Elements at the Molecular Level)
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