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Molecular Cell Jun 2024RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here,...
RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites. hnRNPM preferentially binds at intronic LINEs to repress pseudo splice site usage for cryptic splicing. Remarkably, cryptic exons can generate long dsRNAs through base-pairing of inverted ALU transposable elements interspersed among LINEs and consequently trigger an interferon response, a well-known antiviral defense mechanism. Significantly, hnRNPM-deficient tumors show upregulated interferon-associated pathways and elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity by repressing cryptic splicing and suggest that targeting hnRNPM in tumors may be used to trigger an inflammatory immune response, thereby boosting cancer surveillance.
Topics: Humans; Heterogeneous-Nuclear Ribonucleoprotein Group M; RNA, Double-Stranded; Introns; RNA Splicing; Long Interspersed Nucleotide Elements; Interferons; Animals; HEK293 Cells; Mice; Transcriptome; Exons; RNA Splice Sites; Alu Elements
PubMed: 38815579
DOI: 10.1016/j.molcel.2024.05.004 -
Microbial Genomics May 2024is an emerging human enteric pathogen. However, the genomic features and virulence genes of strains from human gastroenteritis and other sources have not been fully...
Analysis of global genomes revealed that strains carrying T6SS are more common in human gastroenteritis than in environmental sources and are often phylogenetically related.
is an emerging human enteric pathogen. However, the genomic features and virulence genes of strains from human gastroenteritis and other sources have not been fully elucidated. Here, we conducted a genomic analysis of 565 global strains isolated from different sources, including 261 strains isolated from faecal samples of gastroenteritis patients, of which 18 genomes were sequenced in this study. The presence of bacterial virulence genes and secretion systems in strains from different sources was compared, and the phylogenetic relationship of strains was assessed based on the core genome. The complete genome of strain A20-9 isolated from a gastroenteritis patient was obtained in this study, from which 300 putative virulence factors and a T4SS-encoding plasmid, pAC, were identified. Genes encoding T4SS were also identified in a novel genomic island, ACI-1, from other T4SS-positive strains. The prevalence of T4SS was significantly lower in strains from gastroenteritis patients than in environmental strains (3 %, <0.0001 vs 14 %, <0.01). Conversely, the prevalence of T6SS was significantly higher in strains isolated from gastroenteritis patients than in environmental strains (25 %, <0.05 vs 13 %, <0.01). Four phylogenetic clusters were formed based on the core genome of 565 . strains, and strains carrying T6SS often showed close phylogenetic relationships. T3SS, aerolysin and thermostable cytotonic enterotoxin were absent in all 565 . strains. Our findings provide novel information on the genomic features of and suggest that T6SS may play a role in -induced human gastroenteritis.
Topics: Gastroenteritis; Humans; Phylogeny; Genome, Bacterial; Aeromonas caviae; Virulence Factors; Type VI Secretion Systems; Feces; Gram-Negative Bacterial Infections; Genomic Islands; Plasmids
PubMed: 38814176
DOI: 10.1099/mgen.0.001258 -
Nature Communications May 2024Bacterial pathogens carrying multidrug resistance (MDR) plasmids are a major threat to human health. The acquisition of antibiotic resistance genes (ARGs) in plasmids is...
Bacterial pathogens carrying multidrug resistance (MDR) plasmids are a major threat to human health. The acquisition of antibiotic resistance genes (ARGs) in plasmids is often facilitated by mobile genetic elements that copy or translocate ARGs between DNA molecules. The agglomeration of mobile elements in plasmids generates resistance islands comprising multiple ARGs. However, whether the emergence of resistance islands is restricted to specific MDR plasmid lineages remains understudied. Here we show that the agglomeration of ARGs in resistance islands is biased towards specific large plasmid lineages. Analyzing 6784 plasmids in 2441 Escherichia, Salmonella, and Klebsiella isolates, we quantify that 84% of the ARGs in MDR plasmids are found in resistance islands. We furthermore observe rapid evolution of ARG combinations in resistance islands. Most regions identified as resistance islands are shared among closely related plasmids but rarely among distantly related plasmids. Our results suggest the presence of barriers for the dissemination of ARGs between plasmid lineages, which are related to plasmid genetic properties, host range and the plasmid evolutionary history. The agglomeration of ARGs in plasmids is attributed to the workings of mobile genetic elements that operate within the framework of existing plasmid lineages.
Topics: Plasmids; Evolution, Molecular; Salmonella; Anti-Bacterial Agents; Humans; Drug Resistance, Multiple, Bacterial; Klebsiella; Genomic Islands; Escherichia coli; Interspersed Repetitive Sequences
PubMed: 38811529
DOI: 10.1038/s41467-024-48352-8 -
Polish Journal of Microbiology Jun 2024is a non-fermentative Gram-negative bacterium that can cause nosocomial infections in critically ill patients. Carbapenem-resistant (CRAB) has spread rapidly in...
is a non-fermentative Gram-negative bacterium that can cause nosocomial infections in critically ill patients. Carbapenem-resistant (CRAB) has spread rapidly in clinical settings and has become a key concern. The main objective of this study was to identify the distribution of integrons and biofilm-formation-related virulence genes in CRAB isolates. A total of 269 isolates (219 isolates of CRAB and 50 isolates of carbapenem-sensitive (CSAB)) were collected. Carbapenemase genes ( , , , , and ) and biofilm-formation-related virulence genes (, , , and ) were screened with PCR. Class 1 integron was screened with PCR, and common promoters and gene cassette arrays were determined with restriction pattern analysis combined with primer walking sequencing. Whole-genome sequencing was conducted, and data were analyzed for a -negative isolate. All 219 CRAB isolates were negative for , , , and , while was detected in 218 isolates. The detection rates for , , , and in 219 CRAB were 93.15%, 63.93%, 88.13%, and 77.63%, respectively. Class 1 integron was detected in 75 CRAB (34.25%) and in 3 CSAB. The single gene cassette array with relatively strong PcH2 promoter was detected in class 1 integrons. The -negative CRAB isolate was revealed to be a new sequence type (Oxford 3272, Pasteur 2520) carrying , , and . In conclusion, was the main reason for CRAB's resistance to carbapenems. A new (Oxford 3272, Pasteur 2520) CRAB sequence type carrying the , , and was reported.
Topics: Acinetobacter baumannii; beta-Lactamases; Integrons; Biofilms; Bacterial Proteins; Acinetobacter Infections; Humans; Anti-Bacterial Agents; Carbapenems; Microbial Sensitivity Tests
PubMed: 38808771
DOI: 10.33073/pjm-2024-017 -
Virulence Dec 2024() is a bacterial pathogen responsible for a range of infections in humans and various animal hosts, causing significant economic losses in farming. Integrative and...
() is a bacterial pathogen responsible for a range of infections in humans and various animal hosts, causing significant economic losses in farming. Integrative and conjugative elements (ICEs) are important horizontal gene transfer elements, potentially enabling host bacteria to enhance adaptability by acquiring multiple functional genes. However, the understanding of ICEs in and their impact on the transmission of this pathogen remains limited. In this study, 42 poultry-sourced genomes obtained by high-throughput sequencing together with 393 publicly available genomes were used to analyse the horizontal transfer of ICEs. Eighty-two ICEs were identified in , including SXT/R391 and Tn916 subtypes, as well as three subtypes of ICE1056 family, with the latter being widely prevalent in and carrying multiple resistance genes. The correlations between insertion sequences and resistant genes in ICEs were also identified, and some ICEs introduced the carbapenem gene and the bleomycin gene to . Phylogenetic and collinearity analyses of these bioinformatics found that ICEs in were transmitted vertically and horizontally and have evolved with host specialization. These findings provide insight into the transmission and evolution mode of ICEs in and highlight the importance of understanding these elements for controlling the spread of antibiotic resistance.
Topics: Pasteurella multocida; Gene Transfer, Horizontal; Animals; Phylogeny; Pasteurella Infections; Genome, Bacterial; DNA Transposable Elements; Conjugation, Genetic; Evolution, Molecular; Poultry; Prevalence; High-Throughput Nucleotide Sequencing
PubMed: 38808732
DOI: 10.1080/21505594.2024.2359467 -
Scientific Reports May 2024Salmonella enterica is a pathogenic bacterium known for causing severe typhoid fever in humans, making it important to study due to its potential health risks and...
Salmonella enterica is a pathogenic bacterium known for causing severe typhoid fever in humans, making it important to study due to its potential health risks and significant impact on public health. This study provides evolutionary classification of proteins from Salmonella enterica pangenome. We classified 17,238 domains from 13,147 proteins from 79,758 Salmonella enterica strains and studied in detail domains of 272 proteins from 14 characterized Salmonella pathogenicity islands (SPIs). Among SPIs-related proteins, 90 proteins function in the secretion machinery. 41% domains of SPI proteins have no previous sequence annotation. By comparing clinical and environmental isolates, we identified 3682 proteins that are overrepresented in clinical group that we consider as potentially pathogenic. Among domains of potentially pathogenic proteins only 50% domains were annotated by sequence methods previously. Moreover, 36% (1330 out of 3682) of potentially pathogenic proteins cannot be classified into Evolutionary Classification of Protein Domains database (ECOD). Among classified domains of potentially pathogenic proteins the most populated homology groups include helix-turn-helix (HTH), Immunoglobulin-related, and P-loop domains-related. Functional analysis revealed overrepresentation of these protein in biological processes related to viral entry into host cell, antibiotic biosynthesis, DNA metabolism and conformation change, and underrepresentation in translational processes. Analysis of the potentially pathogenic proteins indicates that they form 119 clusters or novel potential pathogenicity islands (NPPIs) within the Salmonella genome, suggesting their potential contribution to the bacterium's virulence. One of the NPPIs revealed significant overrepresentation of potentially pathogenic proteins. Overall, our analysis revealed that identified potentially pathogenic proteins are poorly studied.
Topics: Genomic Islands; Salmonella enterica; Bacterial Proteins; Genome, Bacterial; Humans; Protein Domains
PubMed: 38806511
DOI: 10.1038/s41598-024-60991-x -
Genomics Jul 2024Cassava, a crucial tropical crop, faces challenges from cold stress, necessitating an exploration of its molecular response. Here, we investigated the role of DNA...
Cassava, a crucial tropical crop, faces challenges from cold stress, necessitating an exploration of its molecular response. Here, we investigated the role of DNA methylation in moderating the response to moderate cold stress (10 °C) in cassava. Using whole-genome bisulfite sequencing, we examined DNA methylation patterns in leaf blades and petioles under control conditions, 5 h, and 48 h of cold stress. Tissue-specific responses were observed, with leaf blades exhibiting subtle changes, while petioles displayed a pronounced decrease in methylation levels under cold stress. We identified cold stress-induced differentially methylated regions (DMRs) that demonstrated both tissue and treatment specificity. Importantly, these DMRs were enriched in genes with altered expression, implying functional relevance. The cold-response transcription factor ERF105 associated with DMRs emerged as a significant and conserved regulator across tissues and treatments. Furthermore, we investigated DNA methylation dynamics in transposable elements, emphasizing the sensitivity of MITEs with bHLH binding motifs to cold stress. These findings provide insights into the epigenetic regulation of response to cold stress in cassava, contributing to an understanding of the molecular mechanisms underlying stress adaptation in this tropical plant.
Topics: Manihot; DNA Methylation; Cold-Shock Response; Plant Proteins; Gene Expression Regulation, Plant; Epigenesis, Genetic; Plant Leaves; DNA Transposable Elements; Transcription Factors
PubMed: 38806102
DOI: 10.1016/j.ygeno.2024.110871 -
BMC Microbiology May 2024Schaalia species are primarily found among the oral microbiota of humans and other animals. They have been associated with various infections through their involvement... (Comparative Study)
Comparative Study
Genome characterisation and comparative analysis of Schaalia dentiphila sp. nov. and its subspecies, S. dentiphila subsp. denticola subsp. nov., from the human oral cavity.
BACKGROUND
Schaalia species are primarily found among the oral microbiota of humans and other animals. They have been associated with various infections through their involvement in biofilm formation, modulation of host responses, and interaction with other microorganisms. In this study, two strains previously indicated as Actinomyces spp. were found to be novel members of the genus Schaalia based on their whole genome sequences.
RESULTS
Whole-genome sequencing revealed both strains with a genome size of 2.3 Mbp and GC contents of 65.5%. Phylogenetics analysis for taxonomic placement revealed strains NCTC 9931 and C24 as distinct species within the genus Schaalia. Overall genome-relatedness indices including digital DNA-DNA hybridization (dDDH), and average nucleotide/amino acid identity (ANI/AAI) confirmed both strains as distinct species, with values below the species boundary thresholds (dDDH < 70%, and ANI and AAI < 95%) when compared to nearest type strain Schaalia odontolytica NCTC 9935. Pangenome and orthologous analyses highlighted their differences in gene properties and biological functions compared to existing type strains. Additionally, the identification of genomic islands (GIs) and virulence-associated factors indicated their genetic diversity and potential adaptive capabilities, as well as potential implications for human health. Notably, CRISPR-Cas systems in strain NCTC 9931 underscore its adaptive immune mechanisms compared to strain C24.
CONCLUSIONS
Based on these findings, strain NCTC 9931 (= ATCC 17982 = DSM 43331 = CIP 104728 = CCUG 18309 = NCTC 14978 = CGMCC 1.90328) represents a novel species, for which the name Schaalia dentiphila subsp. dentiphila sp. nov. subsp. nov. is proposed, while strain C24 (= NCTC 14980 = CGMCC 1.90329) represents a distinct novel subspecies, for which the name Schaalia dentiphila subsp. denticola. subsp. nov. is proposed. This study enriches our understanding of the genomic diversity of Schaalia species and paves the way for further investigations into their roles in oral health.
SIGNIFICANCE
This research reveals two Schaalia strains, NCTC 9931 and C24, as novel entities with distinct genomic features. Expanding the taxonomic framework of the genus Schaalia, this study offers a critical resource for probing the metabolic intricacies and resistance patterns of these bacteria. This work stands as a cornerstone for microbial taxonomy, paving the way for significant advances in clinical diagnostics.
Topics: Humans; Genome, Bacterial; Mouth; Phylogeny; Base Composition; Whole Genome Sequencing; DNA, Bacterial; Genomic Islands; Nucleic Acid Hybridization
PubMed: 38802738
DOI: 10.1186/s12866-024-03346-w -
MedRxiv : the Preprint Server For... May 2024DNA repetitive sequences (or repeats) comprise over 50% of the human genome and have a crucial regulatory role, specifically regulating transcription machinery. The...
DNA repetitive sequences (or repeats) comprise over 50% of the human genome and have a crucial regulatory role, specifically regulating transcription machinery. The human brain is the tissue with the highest detectable repeat expression and dysregulations on the repeat activity are related to several neurological and neurodegenerative disorders, as repeat-derived products can stimulate a pro-inflammatory response. Even so, it is unclear how repeat expression acts on the aging neurotypical brain. Here, we leverage a large postmortem transcriptome cohort spanning the human lifespan to assess global repeat expression in the neurotypical brain. We identified 21,696 differentially expressed repeats (DERs) that varied across seven age bins (Prenatal; 0-15; 16-29; 30-39; 40-49; 50-59; 60+) across the caudate nucleus (n=271), dorsolateral prefrontal cortex (n=304), and hippocampus (n=310). Interestingly, we found that long interspersed nuclear elements and long terminal repeats (LTRs) DERs were the most abundant repeat families when comparing infants to early adolescence (0-15) with older adults (60+). Of these differentially regulated LTRs, we identified 17 shared across all brain regions, including increased expression of HERV-K-int in older adult brains (60+). Co-expression analysis from each of the three brain regions also showed repeats from the HERV subfamily were intramodular hubs in its subnetworks. While we do not observe a strong global relationship between repeat expression and age, we identified HERV-K as a repeat signature associated with the aging neurotypical brain. Our study is the first global assessment of repeat expression in the neurotypical brain.
PubMed: 38798538
DOI: 10.1101/2024.05.17.24307184 -
Viruses Apr 2024Transposons are integral genome constituents that can be domesticated for host functions, but they also represent a significant threat to genome stability. Transposon... (Review)
Review
Transposons are integral genome constituents that can be domesticated for host functions, but they also represent a significant threat to genome stability. Transposon silencing is especially critical in the germline, which is dedicated to transmitting inherited genetic material. The small Piwi-interacting RNAs (piRNAs) have a deeply conserved function in transposon silencing in the germline. piRNA biogenesis and function are particularly well understood in , but some fundamental mechanisms remain elusive and there is growing evidence that the pathway is regulated in response to genotoxic and environmental stress. Here, we review transposon regulation by piRNAs and the piRNA pathway regulation in response to stress, focusing on the female germline.
Topics: Animals; DNA Transposable Elements; RNA, Small Interfering; Germ Cells; Gene Silencing; Drosophila melanogaster; Stress, Physiological; Female; Drosophila; Piwi-Interacting RNA
PubMed: 38793595
DOI: 10.3390/v16050714