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Trends in Microbiology Feb 2021There has been an explosion of metagenomic data representing human, animal, and environmental microbiomes. This provides an unprecedented opportunity for comparative and... (Review)
Review
There has been an explosion of metagenomic data representing human, animal, and environmental microbiomes. This provides an unprecedented opportunity for comparative and longitudinal studies of many functional aspects of the microbiome that go beyond taxonomic classification, such as profiling genetic determinants of antimicrobial resistance, interactions with the host, potentially clinically relevant functions, and the role of mobile genetic elements (MGEs). One of the most important but least studied of these aspects are the MGEs, collectively referred to as the 'mobilome'. Here we elaborate on the benefits and limitations of using different metagenomic protocols, discuss the relative merits of various sequencing technologies, and highlight relevant bioinformatics tools and pipelines to predict the presence of MGEs and their microbial hosts.
Topics: Animals; Bacteria; Humans; Interspersed Repetitive Sequences; Metagenome; Metagenomics; Microbiota
PubMed: 32448763
DOI: 10.1016/j.tim.2020.05.003 -
Science (New York, N.Y.) Apr 2022Transposons become a focus of speculation and scrutiny in biomedical research.
Transposons become a focus of speculation and scrutiny in biomedical research.
Topics: DNA Transposable Elements; Repetitive Sequences, Nucleic Acid
PubMed: 35446653
DOI: 10.1126/science.abl7399 -
Cells May 2021The HSP90 protein is a molecular chaperone intensively studied for its role in numerous cellular processes both under physiological and stress conditions. This protein... (Review)
Review
The HSP90 protein is a molecular chaperone intensively studied for its role in numerous cellular processes both under physiological and stress conditions. This protein acts on a wide range of substrates with a well-established role in cancer and neurological disorders. In this review, we focused on the involvement of HSP90 in the silencing of transposable elements and in the genomic integrity maintenance. The common feature of transposable elements is the potential jumping in new genomic positions, causing chromosome structure rearrangements, gene mutations, and influencing gene expression levels. The role of HSP90 in the control of these elements is evolutionarily conserved and opens new perspectives in the HSP90-related mechanisms underlying human disorders. Here, we discuss the hypothesis that its role in the piRNA pathway regulating transposons may be implicated in the onset of neurological diseases.
Topics: Animals; DNA Transposable Elements; Evolution, Molecular; Genomic Instability; HSP90 Heat-Shock Proteins; Humans
PubMed: 34064379
DOI: 10.3390/cells10051096 -
In Vivo (Athens, Greece) 2021Retroelements are genetic mobile elements, expressed during male and female gamete differentiation. Retrotransposons are normally regulated by the methylation machinery,... (Review)
Review
Retroelements are genetic mobile elements, expressed during male and female gamete differentiation. Retrotransposons are normally regulated by the methylation machinery, chromatin modifications, non-coding RNAs, and transcription factors, while retrotransposition control is of vital importance in cellular proliferation and differentiation process. Retrotransposition requires a transcription step, by a cellular RNA polymerase, followed by reverse transcription of an RNA intermediate to cDNA and its integration into a new genomic locus. Long interspersed elements (LINEs), human endogenous retroviruses (HERVs), short interspersed elements (SINEs) and SINE-VNTR-Alu elements (SVAs) constitute about half of the human genome, play a crucial role in genome organization, structure and function and interfere with several biological procedures. In this mini review, we discuss recent data regarding retroelement expression (LINE-1, HERVK-10, SVA and VL30) and retrotransposition events in mammalian oocytes and spermatozoa, as well as the importance of their impact on human and mouse preimplantation embryo development.
Topics: Alu Elements; Animals; Female; Humans; Long Interspersed Nucleotide Elements; Male; Mice; Oocytes; Retroelements; Short Interspersed Nucleotide Elements
PubMed: 34182464
DOI: 10.21873/invivo.12458 -
Nucleic Acids Research Aug 2021Mobile genetic elements have been harnessed for gene transfer for a wide variety of applications including generation of stable cell lines, recombinant protein...
Mobile genetic elements have been harnessed for gene transfer for a wide variety of applications including generation of stable cell lines, recombinant protein production, creation of transgenic animals, and engineering cell and gene therapy products. The piggyBac transposon family includes transposase or transposase-like proteins from a variety of species including insect, bat and human. Recently, human piggyBac transposable element derived 5 (PGBD5) protein was reported to be able to transpose piggyBac transposons in human cells raising possible safety concerns for piggyBac-mediated gene transfer applications. We evaluated three piggyBac-like proteins across species including piggyBac (insect), piggyBat (bat) and PGBD5 (human) for their ability to mobilize piggyBac transposons in human cells. We observed a lack of cross-species transposition activity. piggyBac and piggyBat activity was restricted to their cognate transposons. PGBD5 was unable to mobilize piggyBac transposons based on excision, colony count and plasmid rescue analysis, and it was unable to bind piggyBac terminal repeats. Within the piggyBac family, we observed a lack of cross-species activity and found that PGBD5 was unable to bind, excise or integrate piggyBac transposons in human cells. Transposition activity appears restricted within species within the piggyBac family of mobile genetic elements.
Topics: Animals; Cell Line; DNA Transposable Elements; Genetic Vectors; Humans; Interspersed Repetitive Sequences; Mutagenesis, Insertional; Plasmids; Transcription Factors; Transposases
PubMed: 34232995
DOI: 10.1093/nar/gkab578 -
Genes Feb 2020Cas3 has essential functions in CRISPR immunity but its other activities and roles, in vitro and in cells, are less widely known. We offer a concise review of the latest... (Review)
Review
Cas3 has essential functions in CRISPR immunity but its other activities and roles, in vitro and in cells, are less widely known. We offer a concise review of the latest understanding and questions arising from studies of Cas3 mechanism during CRISPR immunity, and highlight recent attempts at using Cas3 for genetic editing. We then spotlight involvement of Cas3 in other aspects of cell biology, for which understanding is lacking-these focus on CRISPR systems as regulators of cellular processes in addition to defense against mobile genetic elements.
Topics: Clustered Regularly Interspaced Short Palindromic Repeats; DNA Helicases; Gene Editing; Interspersed Repetitive Sequences; Models, Molecular; Protein Conformation
PubMed: 32085454
DOI: 10.3390/genes11020208 -
Cell Reports Jul 2023Prokaryotic adaptation is strongly influenced by the horizontal acquisition of beneficial traits via mobile genetic elements (MGEs), such as viruses/bacteriophages and... (Review)
Review
Prokaryotic adaptation is strongly influenced by the horizontal acquisition of beneficial traits via mobile genetic elements (MGEs), such as viruses/bacteriophages and plasmids. However, MGEs can also impose a fitness cost due to their often parasitic nature and differing evolutionary trajectories. In response, prokaryotes have evolved diverse immune mechanisms against MGEs. Recently, our understanding of the abundance and diversity of prokaryotic immune systems has greatly expanded. These defense systems can degrade the invading genetic material, inhibit genome replication, or trigger abortive infection, leading to population protection. In this review, we highlight these strategies, focusing on the most recent discoveries. The study of prokaryotic defenses not only sheds light on microbial evolution but also uncovers novel enzymatic activities with promising biotechnological applications.
Topics: Prokaryotic Cells; Plasmids; Bacteriophages; Genome; Interspersed Repetitive Sequences
PubMed: 37347666
DOI: 10.1016/j.celrep.2023.112672 -
Journal of Molecular Biology Apr 2023CRISPR-Cas are prokaryotic defence systems that provide protection against invasion by mobile genetic elements (MGE), including bacteriophages. MGE can overcome... (Review)
Review
CRISPR-Cas are prokaryotic defence systems that provide protection against invasion by mobile genetic elements (MGE), including bacteriophages. MGE can overcome CRISPR-Cas defences by encoding anti-CRISPR (Acr) proteins. These proteins are produced in the early stages of the infection and inhibit the CRISPR-Cas machinery to allow phage replication. While research on Acr has mainly focused on their discovery, structure and mode of action, and their applications in biotechnology, the impact of Acr on the ecology of MGE as well as on the coevolution with their bacterial hosts only begins to be unravelled. In this review, we summarise our current understanding on the distribution of anti-CRISPR genes in MGE, the ecology of phages encoding Acr, and their coevolution with bacterial defence mechanisms. We highlight the need to use more diverse and complex experimental models to better understand the impact of anti-CRISPR in MGE-host interactions.
Topics: Bacteria; Bacteriophages; CRISPR-Cas Systems; Evolution, Molecular; Models, Theoretical; Viral Proteins; Interspersed Repetitive Sequences
PubMed: 36690071
DOI: 10.1016/j.jmb.2023.167974 -
Microbial Biotechnology Jan 2024Mobile genetic elements (MGEs) are crucial for horizontal gene transfer (HGT) in bacteria and facilitate their rapid evolution and adaptation. MGEs include plasmids,... (Review)
Review
Mobile genetic elements (MGEs) are crucial for horizontal gene transfer (HGT) in bacteria and facilitate their rapid evolution and adaptation. MGEs include plasmids, integrative and conjugative elements, transposons, insertion sequences and bacteriophages. Notably, the spread of antimicrobial resistance genes (ARGs), which poses a serious threat to public health, is primarily attributable to HGT through MGEs. This mini-review aims to provide an overview of the mechanisms by which MGEs mediate HGT in microbes. Specifically, the behaviour of conjugative plasmids in different environments and conditions was discussed, and recent methodologies for tracing the dynamics of MGEs were summarised. A comprehensive understanding of the mechanisms underlying HGT and the role of MGEs in bacterial evolution and adaptation is important to develop strategies to combat the spread of ARGs.
Topics: Interspersed Repetitive Sequences; Gene Transfer, Horizontal; Plasmids; Bacteria; Bacteriophages; Anti-Bacterial Agents
PubMed: 38226780
DOI: 10.1111/1751-7915.14408 -
Epigenetics & Chromatin Jun 2021DNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability... (Review)
Review
BACKGROUND
DNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability (including chromosome stability) by controlling both gene expression and chromatin structure. Therefore, the onset of an incorrect pattern of DNA methylation is potentially dangerous for the cells. This is particularly important with respect to repetitive elements, which constitute the third of the human genome.
MAIN BODY
Repetitive sequences are involved in several cell processes, however, due to their intrinsic nature, they can be a source of genome instability. Thus, most repetitive elements are usually methylated to maintain a heterochromatic, repressed state. Notably, there is increasing evidence showing that repetitive elements (satellites, long interspersed nuclear elements (LINEs), Alus) are frequently hypomethylated in various of human pathologies, from cancer to psychiatric disorders. Repetitive sequences' hypomethylation correlates with chromatin relaxation and unscheduled transcription. If these alterations are directly involved in human diseases aetiology and how, is still under investigation.
CONCLUSIONS
Hypomethylation of different families of repetitive sequences is recurrent in many different human diseases, suggesting that the methylation status of these elements can be involved in preservation of human health. This provides a promising point of view towards the research of therapeutic strategies focused on specifically tuning DNA methylation of DNA repeats.
Topics: Chromatin; DNA Methylation; Epigenomics; Humans; Long Interspersed Nucleotide Elements; Repetitive Sequences, Nucleic Acid
PubMed: 34082816
DOI: 10.1186/s13072-021-00400-z