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Trends in Genetics : TIG Nov 2017The duality of group II introns, capable of carrying out both self-splicing and retromobility reactions, is hypothesized to have played a profound role in the evolution... (Review)
Review
The duality of group II introns, capable of carrying out both self-splicing and retromobility reactions, is hypothesized to have played a profound role in the evolution of eukaryotes. These introns likely provided the framework for the emergence of eukaryotic retroelements, spliceosomal introns and other key components of the spliceosome. Group II introns are found in all three domains of life and are therefore considered to be exceptionally successful mobile genetic elements. Initially identified in organellar genomes, group II introns are found in bacteria, chloroplasts, and mitochondria of plants and fungi, but not in nuclear genomes. Although there is no doubt that prokaryotic and organellar group II introns are evolutionary related, there are remarkable differences in survival strategies between them. Furthermore, an evolutionary relationship of group II introns to eukaryotic retroelements, including telomeres, and spliceosomes is unmistakable.
Topics: Bacteria; Eukaryotic Cells; Interspersed Repetitive Sequences; Introns; RNA, Catalytic; Spliceosomes
PubMed: 28818345
DOI: 10.1016/j.tig.2017.07.009 -
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 -
Current Opinion in Microbiology Aug 2017Self-splicing introns and inteins are often mobile at the level of the genome. Although these RNA and protein elements, respectively, are generally considered to be... (Review)
Review
Self-splicing introns and inteins are often mobile at the level of the genome. Although these RNA and protein elements, respectively, are generally considered to be selfish parasites, group I and group II introns and inteins can be triggered by environmental cues to splice and/or to mobilize. These cues include stressors such as oxidizing agents, reactive oxygen and nitrogen species, starvation, temperature, osmolarity and DNA damage. Their sensitivity to these stimuli leads to a carefully choreographed dance between the mobile element and its host that is in tune with the cellular environment. This responsiveness to a changing milieu provides strong evidence that these diverse, self-splicing mobile elements have adapted to react to prevailing conditions, to the potential advantage of both the element and its host.
Topics: Adaptation, Biological; Environmental Exposure; Gene Expression Regulation; Inteins; Interspersed Repetitive Sequences; Introns; RNA Splicing
PubMed: 28482231
DOI: 10.1016/j.mib.2017.04.003 -
Experimental Hematology Oct 2016Understanding transformation mechanisms other than genetic aberrations has recently captured the attention of cancer researchers. To date, the role of transposable... (Review)
Review
Understanding transformation mechanisms other than genetic aberrations has recently captured the attention of cancer researchers. To date, the role of transposable elements (TEs) in tumor development remains largely undefined. However, an increasing number of studies have reported that loss of epigenetic control causes TE reactivation and consequent oncogenic transcription. Here, we discuss principal examples of TEs-driven oncogenesis. Available data suggest that long terminal repeats and long interspersed nuclear elements play a pivotal role as alternative promoters. These findings provide definitive experimental evidence that repetitive elements are a powerful underestimated force toward oncogenesis and open the possibility to new therapeutic treatments.
Topics: Animals; Cell Transformation, Neoplastic; DNA Transposable Elements; Epigenesis, Genetic; Humans; Long Interspersed Nucleotide Elements; Neoplasms; Promoter Regions, Genetic; Terminal Repeat Sequences
PubMed: 27377925
DOI: 10.1016/j.exphem.2016.06.251 -
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 -
Current Opinion in Microbiology Jun 2017Clustered, regularly interspaced, short, palindromic repeats (CRISPR) loci, together with their CRISPR-associated (Cas) proteins, provide bacteria and archaea with... (Review)
Review
Clustered, regularly interspaced, short, palindromic repeats (CRISPR) loci, together with their CRISPR-associated (Cas) proteins, provide bacteria and archaea with adaptive immunity against invasion by bacteriophages, plasmids, and other mobile genetic elements. These host defenses impart selective pressure on phages and mobile elements to evolve countermeasures against CRISPR immunity. As a consequence of this pressure, phages and mobile elements have evolved 'anti-CRISPR' proteins that function as direct inhibitors of diverse CRISPR-Cas effector complexes. Some of these CRISPR-Cas complexes can be deployed as genome engineering platforms, and anti-CRISPRs could therefore be useful in exerting spatial, temporal, or conditional control over genome editing and related applications. Here we describe the discovery of anti-CRISPRs, the range of CRISPR-Cas systems that they inhibit, their mechanisms of action, and their potential utility in biotechnology.
Topics: Bacteria; Bacteriophages; CRISPR-Cas Systems; Evolution, Molecular; Host-Parasite Interactions; Interspersed Repetitive Sequences
PubMed: 28668720
DOI: 10.1016/j.mib.2017.06.003 -
Mechanisms of Ageing and Development Sep 2018Endogenous retroelements, transposons that mobilize through RNA intermediates, include some of the most abundant repetitive sequences of the human genome, such as Alu... (Review)
Review
Endogenous retroelements, transposons that mobilize through RNA intermediates, include some of the most abundant repetitive sequences of the human genome, such as Alu and LINE-1 sequences, and human endogenous retroviruses. Recent discoveries demonstrate that these mobile genetic elements not only act as intragenomic parasites, but also exert regulatory roles in living cells. The risk of genomic instability represented by endogenous retroelements is normally counteracted by a series of epigenetic control mechanisms which include, among the most important, CpG DNA methylation. Indeed, most of the genomic CpG sites subjected to DNA methylation in the nuclear DNA are carried by these repetitive elements. As other parts of the genome, endogenous retroelements and other transposable elements are subjected to deep epigenetic alterations during aging, repeatedly observed in the context of organismal and cellular senescence, in human and other species. This review summarizes the current status of knowledge about the epigenetic alterations occurring in this large, non-genic portion of the genome in aging and age-related conditions, with a focus on the causes and the possible functional consequences of these alterations.
Topics: Aging; Alu Elements; Animals; Cellular Senescence; CpG Islands; DNA Methylation; Epigenesis, Genetic; Humans; Long Interspersed Nucleotide Elements
PubMed: 29458070
DOI: 10.1016/j.mad.2018.02.002 -
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