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PLoS Genetics Jun 2024Long interspersed element 1 (LINE-1; L1) are a family of transposons that occupy ~17% of the human genome. Though a small number of L1 copies remain capable of...
Long interspersed element 1 (LINE-1; L1) are a family of transposons that occupy ~17% of the human genome. Though a small number of L1 copies remain capable of autonomous transposition, the overwhelming majority of copies are degenerate and immobile. Nevertheless, both mobile and immobile L1s can exert pleiotropic effects (promoting genome instability, inflammation, or cellular senescence) on their hosts, and L1's contributions to aging and aging diseases is an area of active research. However, because of the cell type-specific nature of transposon control, the catalogue of L1 regulators remains incomplete. Here, we employ an eQTL approach leveraging transcriptomic and genomic data from the GEUVADIS and 1000Genomes projects to computationally identify new candidate regulators of L1 RNA levels in lymphoblastoid cell lines. To cement the role of candidate genes in L1 regulation, we experimentally modulate the levels of top candidates in vitro, including IL16, STARD5, HSD17B12, and RNF5, and assess changes in TE family expression by Gene Set Enrichment Analysis (GSEA). Remarkably, we observe subtle but widespread upregulation of TE family expression following IL16 and STARD5 overexpression. Moreover, a short-term 24-hour exposure to recombinant human IL16 was sufficient to transiently induce subtle, but widespread, upregulation of L1 subfamilies. Finally, we find that many L1 expression-associated genetic variants are co-associated with aging traits across genome-wide association study databases. Our results expand the catalogue of genes implicated in L1 RNA control and further suggest that L1-derived RNA contributes to aging processes. Given the ever-increasing availability of paired genomic and transcriptomic data, we anticipate this new approach to be a starting point for more comprehensive computational scans for regulators of transposon RNA levels.
Topics: Humans; Quantitative Trait Loci; Long Interspersed Nucleotide Elements; Genome, Human; Transcriptome; RNA; Gene Expression Regulation; Cell Line; Lymphocytes
PubMed: 38848448
DOI: 10.1371/journal.pgen.1011311 -
Science Advances Jun 2024Olfaction is essential for complex social behavior in insects. To discriminate complex social cues, ants evolved an expanded number of () genes. Mutations in the...
Olfaction is essential for complex social behavior in insects. To discriminate complex social cues, ants evolved an expanded number of () genes. Mutations in the obligate odorant co-receptor gene lead to the loss of ~80% of the antennal lobe glomeruli in the jumping ant . However, the cellular mechanism remains unclear. Here, we demonstrate massive apoptosis of odorant receptor neurons (ORNs) in the mid to late stages of pupal development, possibly due to ER stress in the absence of Orco. Further bulk and single-nucleus transcriptome analysis shows that, although most -expressing ORNs die in mutants, a small proportion of them survive: They express () genes that form IR complexes. In addition, we found that some genes are expressed in mechanosensory neurons and nonneuronal cells, possibly due to leaky regulation from nearby non- genes. Our findings provide a comprehensive overview of ORN development and expression in .
Topics: Animals; Olfactory Receptor Neurons; Ants; Receptors, Odorant; Apoptosis; Mutation; Cell Survival; Insect Proteins; Gene Expression Profiling; Transcriptome
PubMed: 38848359
DOI: 10.1126/sciadv.adk9000 -
Scientific Reports Jun 2024Metagenomics has made it feasible to elucidate the intricacies of the ruminal microbiome and its role in the differentiation of animal production phenotypes of...
Metagenomics has made it feasible to elucidate the intricacies of the ruminal microbiome and its role in the differentiation of animal production phenotypes of significance. The search for mobile genetic elements (MGEs) has taken on great importance, as they play a critical role in the transfer of genetic material between organisms. Furthermore, these elements serve a dual purpose by controlling populations through lytic bacteriophages, thereby maintaining ecological equilibrium and driving the evolutionary progress of host microorganisms. In this study, we aimed to identify the association between ruminal bacteria and their MGEs in Nellore cattle using physical chromosomal links through the Hi-C method. Shotgun metagenomic sequencing and the proximity ligation method ProxiMeta were used to analyze DNA, getting 1,713,111,307 bp, which gave rise to 107 metagenome-assembled genomes from rumen samples of four Nellore cows maintained on pasture. Taxonomic analysis revealed that most of the bacterial genomes belonged to the families Lachnospiraceae, Bacteroidaceae, Ruminococcaceae, Saccharofermentanaceae, and Treponemataceae and mostly encoded pathways for central carbon and other carbohydrate metabolisms. A total of 31 associations between host bacteria and MGE were identified, including 17 links to viruses and 14 links to plasmids. Additionally, we found 12 antibiotic resistance genes. To our knowledge, this is the first study in Brazilian cattle that connect MGEs with their microbial hosts. It identifies MGEs present in the rumen of pasture-raised Nellore cattle, offering insights that could advance biotechnology for food digestion and improve ruminant performance in production systems.
Topics: Animals; Cattle; Rumen; Interspersed Repetitive Sequences; Metagenomics; Metagenome; Microbiota; Gastrointestinal Microbiome; Bacteria; Genome, Bacterial; Phylogeny
PubMed: 38844487
DOI: 10.1038/s41598-024-63951-7 -
PLoS Pathogens Jun 2024Amikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the...
Amikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the family Enterobacterales. Here we show that two gene cassettes located side-by-side in and ancestral integron similar to In37 have been "harvested" by insertion sequence IS26 as a transposon that is widely disseminated among the Enterobacterales. This transposon encodes the enzymes AAC(6')-Ib-cr and OXA-1, reported, respectively, as amikacin and piperacillin/tazobactam resistance mechanisms. However, by studying bloodstream infection isolates from 769 patients from three hospitals serving a population of 1.2 million people in South West England, we show that increased enzyme production due to mutation in an IS26/In37-derived hybrid promoter or, more commonly, increased transposon copy number is required to simultaneously remove these two key therapeutic options; in many cases leaving only the last-resort antibiotic, meropenem. These findings may help improve the accuracy of predicting piperacillin/tazobactam treatment failure, allowing stratification of patients to receive meropenem or piperacillin/tazobactam, which may improve outcome and slow the emergence of meropenem resistance.
Topics: Humans; Anti-Bacterial Agents; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Piperacillin; Amikacin; Microbial Sensitivity Tests; Enterobacteriaceae Infections; Enterobacteriaceae; Integrons; Bacteremia
PubMed: 38843111
DOI: 10.1371/journal.ppat.1012235 -
TAG. Theoretical and Applied Genetics.... Jun 2024Analyze the evolutionary pattern of DNAJ protein genes in the Panicoideae, including pearl millet, to identify and characterize the biological function of PgDNAJ genes...
Analyze the evolutionary pattern of DNAJ protein genes in the Panicoideae, including pearl millet, to identify and characterize the biological function of PgDNAJ genes in pearl millet. Global warming has become a major factor threatening food security and human development. It is urgent to analyze the heat-tolerant mechanism of plants and cultivate crops that are adapted to high temperature conditions. The Panicoideae are the second largest subfamily of the Poaceae, widely distributed in warm temperate and tropical regions. Many of these species have been reported to have strong adaptability to high temperature stress, such as pearl millet, foxtail millet and sorghum. The evolutionary differences in DNAJ protein genes among 12 Panicoideae species and 10 other species were identified and analyzed. Among them, 79% of Panicoideae DNAJ protein genes were associated with retrotransposon insertion. Analysis of the DNAJ protein pan-gene family in six pearl millet accessions revealed that the non-core genes contained significantly more TEs than the core genes. By identifying and analyzing the distribution and types of TEs near the DNAJ protein genes, it was found that the insertion of Copia and Gypsy retrotransposons provided the source of expansion for the DNAJ protein genes in the Panicoideae. Based on the analysis of the evolutionary pattern of DNAJ protein genes in Panicoideae, the PgDNAJ was obtained from pearl millet through identification. PgDNAJ reduces the accumulation of reactive oxygen species caused by high temperature by activating ascorbate peroxidase (APX), thereby improving the heat resistance of plants. In summary, these data provide new ideas for mining potential heat-tolerant genes in Panicoideae, and help to improve the heat tolerance of other crops.
Topics: Pennisetum; Plant Proteins; Phylogeny; HSP40 Heat-Shock Proteins; Gene Expression Regulation, Plant; Retroelements; Poaceae; Evolution, Molecular; Genes, Plant
PubMed: 38836874
DOI: 10.1007/s00122-024-04656-3 -
Molecular Cell Jun 2024The Tn7 family of transposons is notable for its highly regulated integration mechanisms, including programmable RNA-guided transposition. The targeting pathways rely on...
The Tn7 family of transposons is notable for its highly regulated integration mechanisms, including programmable RNA-guided transposition. The targeting pathways rely on dedicated target selection proteins from the TniQ family and the AAA+ adaptor TnsC to recruit and activate the transposase at specific target sites. Here, we report the cryoelectron microscopy (cryo-EM) structures of TnsC bound to the TniQ domain of TnsD from prototypical Tn7 and unveil key regulatory steps stemming from unique behaviors of ATP- versus ADP-bound TnsC. We show that TnsD recruits ADP-bound dimers of TnsC and acts as an exchange factor to release one protomer with exchange to ATP. This loading process explains how TnsC assembles a heptameric ring unidirectionally from the target site. This unique loading process results in functionally distinct TnsC protomers within the ring, providing a checkpoint for target immunity and explaining how insertions at programmed sites precisely occur in a specific orientation across Tn7 elements.
Topics: Cryoelectron Microscopy; DNA Transposable Elements; Adenosine Triphosphate; Transposases; Adenosine Diphosphate; Protein Binding; Bacterial Proteins; Models, Molecular; Protein Multimerization; Binding Sites
PubMed: 38834067
DOI: 10.1016/j.molcel.2024.05.012 -
Molecular Cell Jun 2024CRISPR-associated transposons (CASTs) are mobile genetic elements that co-opt CRISPR-Cas systems for RNA-guided DNA transposition. CASTs integrate large DNA cargos into...
CRISPR-associated transposons (CASTs) are mobile genetic elements that co-opt CRISPR-Cas systems for RNA-guided DNA transposition. CASTs integrate large DNA cargos into the attachment (att) site independently of homology-directed repair and thus hold promise for eukaryotic genome engineering. However, the functional diversity and complexity of CASTs hinder an understanding of their mechanisms. Here, we present the high-resolution cryoelectron microscopy (cryo-EM) structure of the reconstituted ∼1 MDa post-transposition complex of the type V-K CAST, together with different assembly intermediates and diverse TnsC filament lengths, thus enabling the recapitulation of the integration complex formation. The results of mutagenesis experiments probing the roles of specific residues and TnsB-binding sites show that transposition activity can be enhanced and suggest that the distance between the PAM and att sites is determined by the lengths of the TnsB C terminus and the TnsC filament. This singular model of RNA-guided transposition provides a foundation for repurposing the system for genome-editing applications.
Topics: Cryoelectron Microscopy; DNA Transposable Elements; CRISPR-Cas Systems; Binding Sites; Gene Editing; Models, Molecular; RNA, Guide, CRISPR-Cas Systems; Clustered Regularly Interspaced Short Palindromic Repeats; Protein Conformation; Nucleic Acid Conformation
PubMed: 38834066
DOI: 10.1016/j.molcel.2024.05.005 -
Gut Microbes 2024The facultative anaerobic Gram-positive bacterium is a ubiquitous member of the human gut microbiota. However, it has gradually evolved into a pathogenic and multidrug...
The facultative anaerobic Gram-positive bacterium is a ubiquitous member of the human gut microbiota. However, it has gradually evolved into a pathogenic and multidrug resistant lineage that causes nosocomial infections. The establishment of high-level intestinal colonization by enterococci represents a critical step of infection. The majority of current research on has been conducted under aerobic conditions, while limited attention has been given to its physiological characteristics in anaerobic environments, which reflects its natural colonization niche in the gut. In this study, a high-density transposon mutant library containing 26,620 distinct insertion sites was constructed. Tn-seq analysis identified six genes that significantly contribute to growth under anaerobic conditions. Under anaerobic conditions, deletion of (encoding Fe-S cluster assembly protein B) results in more extensive and significant impairments on carbohydrate metabolism compared to aerobic conditions. Consistently, the pathways involved in this utilization-restricted carbohydrates were mostly expressed at significantly lower levels in mutant compared to wild-type under anaerobic conditions. Moreover, deletion of or (encoding pyruvate formate lyase-activating protein A) led to failure of gastrointestinal colonization in mice. These findings contribute to our understanding of the mechanisms by which maintains proliferation under anaerobic conditions and establishes colonization in the gut.
Topics: Enterococcus faecium; Animals; Mice; Bacterial Proteins; Anaerobiosis; Iron-Sulfur Proteins; Gastrointestinal Tract; Gastrointestinal Microbiome; Gram-Positive Bacterial Infections; Humans; DNA Transposable Elements; Carbohydrate Metabolism; Female; Acetyltransferases
PubMed: 38831611
DOI: 10.1080/19490976.2024.2359665 -
Medical Science Monitor : International... Jun 2024BACKGROUND In China, the most prevalent type of CRKP is ST11, but the high-risk clone ST15 has grown in popularity in recent years, posing a serious public health risk....
BACKGROUND In China, the most prevalent type of CRKP is ST11, but the high-risk clone ST15 has grown in popularity in recent years, posing a serious public health risk. Therefore, we investigated the molecular prevalence characteristics of ST15 CRKP detected in a tertiary hospital in Ningbo to understand the current potential regional risk of ST15 CRKP outbreak. MATERIAL AND METHODS We collected and evaluated 18 non-duplicated CRKP strains of ST15 type for antibiotic resistance. Their integrons, virulence genes, and resistance genes were identified using polymerase chain reaction (PCR), and their homology was determined using MALDI-TOF MS. RESULTS The predominant serotype of 18 ST15 CRKP strains was K5. ST15 CRKP exhibited the lowest antimicrobial resistance to Cefoperazone/sulbactam (11.1%), followed by trimethoprim/sulfamethoxazole (22.2%). Resistance gene testing revealed that 14 out of 18 ST15 CRKP strains (77.8%) carried Klebsiella pneumoniae carbapenemase 2 (KPC-2), whereas all ST15 CRKP integrons were of the intI1 type. Furthermore, virulence gene testing revealed that all 18 ST15 CRKP strains carried ybtS, kfu, irp-1, and fyuA genes, followed by the irp-2 gene (17 strains) and entB (16 strains). The homology analysis report showed that 2 clusters had closer affinity, which was mainly concentrated in classes C and D. CONCLUSIONS The ST15 CRKP antibiotic resistance rates demonstrate clear geographical differences in Ningbo. Additionally, some strains carried highly virulent genes, indicating a possible evolution towards carbapenem-resistant highly virulent strains. To reduce the spread of ST15 CRKP, we must rationalize the clinical use of antibiotics and strengthen resistance monitoring to control nosocomial infections.
Topics: China; Klebsiella pneumoniae; Tertiary Care Centers; Humans; Klebsiella Infections; Anti-Bacterial Agents; Carbapenems; Microbial Sensitivity Tests; Prevalence; Integrons; Bacterial Proteins; beta-Lactamases; Drug Resistance, Bacterial; Carbapenem-Resistant Enterobacteriaceae
PubMed: 38831571
DOI: 10.12659/MSM.943596 -
Database : the Journal of Biological... Jun 2024We launched the initial version of FishTEDB in 2018, which aimed to establish an open-source, user-friendly, data-rich transposable element (TE) database. Over the past...
We launched the initial version of FishTEDB in 2018, which aimed to establish an open-source, user-friendly, data-rich transposable element (TE) database. Over the past 5 years, FishTEDB 1.0 has gained approximately 10 000 users, accumulating more than 450 000 interactions. With the unveiling of extensive fish genome data and the increasing emphasis on TE research, FishTEDB needs to extend the richness of data and functions. To achieve the above goals, we introduced 33 new fish species to FishTEDB 2.0, encompassing a wide array of fish belonging to 48 orders. To make the updated database more functional, we added a genome browser to visualize the positional relationship between TEs and genes and the estimated TE insertion time in different species. In conclusion, we released a new version of the fish TE database, FishTEDB 2.0, designed to assist researchers in the future study of TE functions and promote the progress of biological theories related to TEs. Database URL: https://www.fishtedb.com/.
Topics: DNA Transposable Elements; Animals; Fishes; Databases, Genetic; Databases, Nucleic Acid
PubMed: 38829853
DOI: 10.1093/database/baae044