Molecular Genetics and Genomics最新文献

Cyclic Nucleotide-Gated Channel (CNGC) gene consists a large family and plays an important role in plant growth and development, biotic and abiotic stresses, yet their functions in non-model crops like kenaf (Hibiscus cannabinus L.), a highly stress-resistant bast fiber crop, remain poorly understood. To investigate the role in kenaf abiotic stress response and plant development regulation, we characterized the HcCNGC27 gene in kenaf. Our study aimed to elucidate the role of HcCNGC27 in drought stress response and its impact on plant development. HcCNGC27 was identified subcellularly localized to the plasma membrane. Expression analysis showed that HcCNGC27 is ubiquitously expressed across various tissues including roots, stems, leaves, flowers, and seeds, with the highest expression observed in flowers. Importantly, HcCNGC27 was significantly induced under drought stress conditions. To investigate the function of HcCNGC27, we performed virus-induced gene silencing (VIGS) in kenaf and overexpression in Arabidopsis thaliana. Silencing of HcCNGC27 in kenaf resulted in a dwarf phenotype and reduced drought stress tolerance, evidenced by decreased antioxidant enzyme activities, increased reactive oxygen species (ROS) accumulation, and decreased osmoregulatory substances content. Additionally, the expression levels of antioxidant enzyme-related genes and stress-responsive genes were markedly down-regulated in the silenced lines. Conversely, overexpression of HcCNGC27 in Arabidopsis thaliana enhanced drought stress tolerance, characterized by stronger protective enzyme activity, better ROS scavenging capacity, improved osmotic adjustment, higher total chlorophyll content, lower death rate, and significant up-regulation of stress-responsive genes. Moreover, overexpression of HcCNGC27 delayed flowering in Arabidopsis thaliana, as indicated by qRT-PCR analysis showing significant down-regulation of AtFT and AtSOC1 and up-regulation of AtFLC in the overexpression lines compared to wild-type controls. In summary, HcCNGC27 emerges as a dual-function regulator enhancing drought tolerance via ROS scavenging and osmotic adjustment while delaying flowering may through modulation of the FT/SOC1/FLC pathway.

Epigenetic alterations are emerging as a major driver of acquired cisplatin (CDDP) resistance in bladder cancer (BCa). The study investigated whether GSK343, an inhibitor of Enhancer of Zeste Homolog 2 (EZH2), can overcome CDDP resistance in BCa. CDDP-resistant T24 and 5637 cells were treated GSK343 (5, 10, or 20µM) for 48 h. Cell viability was assessed using CCK-8 assays, clonogenic survival using colony formation assays, migration capacity using wound healing (scratch) assays, invasion using Transwell assays, and apoptosis using flow cytometry. CDDP-resistant cells exhibited significantly higher EZH2 and H3K27me3 expression levels than parental T24 and 5637 cells. Treatment with 20 µM GSK343 markedly reduced EZH2 and H3K27me3 expression in resistant cells compared to vehicle control, with greater efficacy than lower concentrations (5 or 10 µM). Following 20 µM GSK343 treatment, resistant cells showed significantly reduced viability, fewer colonies, impaired migration, and decreased invasion compared to vehicle control. Furthermore, the apoptosis rate was significantly increased in resistant cells treated with 20 µM GSK343. The study demonstrates that GSK343 inhibits EZH2-mediated H3K27me3 and overcomes acquired CDDP resistance in BCa cells, suggesting its therapeutic potential for BCa patients with limited benefit from chemotherapy.

Calotropis procera (Akra, 2n = 22) is a fast-growing, fiber-producing, and climate-resilient, yet underexplored for domestication. The significant step forward in the domestication of this invaluable plant species marks the development of a reference genome. The study reveals a chromosome-scale genome that anchors 11 chromosomes, with a reference assembly spanning approximately 202.83 Mb. It contains few repetitive sequences, accounting for only 5% of the total genome. C. procera display a significant pair-orthology dN/dS ratio of nearly 0.2 to 0.25, indicating strong conservation, purifying selection, and resistance to harsh conditions. C. procera experienced phylogenetic relations with familiar sister genera divergent around 38.5 million years ago. The chromosomal structural rearrangement endured alterations throughout divergence due to a synteny interaction with the genomes of A. syriaca. The findings delve into the role of gene families in the adaptive evolutionary processes of C. procera. The study enhanced our comprehension of genome biology, the influence of gene families on adaptation. The genome research is invaluable and will significantly influence the future domestication of C. procera.

Haplotagged variant calling is essential for determining genetic etiologies in hereditary hearing loss (HHL) cases when familial testing is unavailable, and long-read whole-genome sequencing (lrWGS) enables this by outperforming in several key areas: enhanced detection of structural variations (SVs) and precise long-range haplotype phasing. In this study, we enrolled two HL cases from the China Deafness Genetics Consortium (CDGC) cohort, whose genetic tests were previously inconclusive due to a lack of pedigree segregation data. Small variants (including SNVs and InDels) profiles were generated by short-read whole-genome sequencing (srWGS), while SVs were identified and co-phased with small variants using a read-based approach. As a result, 87% and 83% of the chromosomal regions were successfully phased, and reached mean haplotype block lengths up to 661.9 kb and 309.9 kb, respectively. A total of 483 and 434 small variants, along with three and six heterozygous SVs in coding and splice regions of 201 HL-associated genes were phased. Pathogenic interpretations resolved compound heterozygosity in MARVELD2, identifying a pathogenic (P) variant NM_001038603.3:c.782G > A in trans with a novel pathogenic (P) deletion (NM_001038603.3:c.1183-1288_1503 + 195del). Additionally, we identified a known P variant NM_022124.6:c.5369-1G > A, which was oriented in trans with a P deletion NM_022124.6:c.-5-12_67 + 154del in the CDH23 gene. This study demonstrates the clinical utility of integrating srWGS and Nanopore lrWGS for comprehensive variant detection and haplotype determination in HL cases with limited family background details, providing a robust framework for resolving complex genetic etiologies and improving diagnostic precision.

Blackcurrant (Ribes nigrum L.), a nutrient-rich cold-climate berry, accumulates ascorbic acid (AsA) and flavonoids critical for fruit quality, yet their regulatory mechanisms during development remain poorly characterized. This study systematically investigated AsA and flavonoid dynamics across four developmental stages (young, expansion, veraison, ripe) in two contrasting varieties, 'Adelinia' and 'Heifeng', while integrating transcriptomics to elucidate metabolic pathways and regulatory networks. We observed a progressive decline in AsA content during fruit maturation, governed by coordinated regulation of biosynthesis (GDP-L-galactose phosphorylase-driven) and recycling pathways (mediated by monodehydroascorbate reductase). Flavonoid levels peaked at the young fruit stage, sharply decreased during veraison, and showed varietal specificity, with 'Heifeng' exhibiting higher accumulation. Co-expression networks identified 4 core structural genes and 6 transcription factors (TFs) regulating AsA metabolism, alongside 8 structural genes and 9 TFs associated with flavonoid biosynthesis. Comparative analysis of fruit size revealed divergent hormone signaling between varieties, with auxin- and cytokinin-related DEGs in the plant hormone transduction pathway (ko04075) strongly correlated with cell expansion. Photosynthesis-antenna protein pathway genes (ko00196) further contributed to size variation, suggesting energy allocation trade-offs during ripening. These findings advance the molecular understanding of AsA and flavonoid regulation in blackcurrant, highlighting cultivar-specific metabolic strategies. The identified genes and TFs provide actionable targets for breeding programs aimed at enhancing nutritional quality and yield, while insights into hormone signaling offer practical frameworks for optimizing growth regulator applications in cultivation.

Soybean seed width (SW) is a pivotal quantitative trait influencing both seed yield and appearance quality, controlled by a complex interplay of multiple genes and environmental factors. This research was undertaken to identify significant genetic loci and candidate genes associated with SW, thereby facilitating the development of molecular markers crucial for advancing soybean breeding programs. In this study, a four-way recombinant inbred line (FW-RIL) population, derived from the cross of (Kenfeng14 × Kenfeng15) × (Heinong48 × Kenfeng19),¹ alongside a diverse germplasm population (GP) comprising 455 soybean cultivars, served as the genetic material. Phenotypic measurements of SW were meticulously recorded for the FW-RILs across three distinct environments and for the GP across four environments. Subsequent linkage analysis in the FW-RIL population and genome-wide association studies (GWAS) in the GP were conducted to map the quantitative trait loci (QTLs) and quantitative trait nucleotides (QTNs) underlying SW. These analyses successfully identified a total of 51 QTLs and 103 QTNs associated with SW. Furthermore, detailed investigation of seven QTNs attenuation regions located within the consistently detected qSW-7-2 region was performed to predict potential candidate genes. This process led to the selection of three promising genes; Glyma.07G004700, Glyma.07G006300, and Glyma.07G013700 based on the integrated evidence from sequence variation analysis among parental lines, comprehensive haplotype analysis within the mapping populations, and relevant functional annotation. The comprehensive identification of these QTLs, QTNs, and particularly the three prioritized candidate genes, offers significant insights into the genetic control of soybean seed width and provides a robust foundation for the development of effective molecular markers to enhance the efficiency of marker-assisted selection for improved soybean yield.

High mobility group (HMG) proteins, the second most abundant chromatin proteins after histones, play essential roles in eukaryotic gene regulation. Among these, High Mobility Group Box 3 (HMGB3) is critical for DNA repair and has gained prominence in cancer biology due to its involvement in tumorigenesis and cancer progression. This study explores the cellular and molecular mechanisms underlying HMGB3's oncogenic functions, with a focus on its potential as a prognostic biomarker and therapeutic target. We highlight that HMGB3 is frequently overexpressed in tumor tissues and discuss its association with poor clinical outcomes. Furthermore, we examine the ceRNA network and other regulatory pathways influencing HMGB3 expression, emphasizing their implications for RNA-based therapies. By comprehensively reviewing HMGB3's role across multiple cancer types, this work provides insights into novel strategies for targeting HMGB3 to improve cancer treatment efficacy. Our findings underscore the therapeutic potential of modulating HMGB3 expression and pave the way for future research into precision oncology approaches.

Inhibition of the activity of Pma1, a widely conserved P-type proton exporting ATPase, has been shown to extend the chronological lifespan (CLS) in fission yeast Schizosaccharomyces pombe. To develop a specific inhibitor for Pma1 of S. pombe, we focused on Si01, a candidate inhibitor of Saccharomyces cerevisiae Pma1. First, we have established a method for synthesis of Si01 and then investigated its Pma1 inhibitory activity and lifespan extension effect in fission yeast. Second, we also synthesized derivatives of Si01 and determined the minimum structure required for inhibition of S. pombe Pma1. Here we showed that the inhibitory activity of Pma1 correlates with the effect of lifespan extension. Si01 reduced the activity of purified Pma1 protein and extended the CLS of not only fission yeast but also budding yeast. These results provide a molecular basis for understanding the mechanism of Pma1 inhibition and the potential for developing molecules that regulate lifespan.

Myogenesis, a multistep process involving myoblast proliferation and differentiation, is critical for determining the economic value of beef cattle. While long noncoding RNAs (lncRNAs) are known to regulate myoblast proliferation, their specific mechanisms remain unclear. This study investigates the role of lncBNIP3 in bovine myoblast proliferation and examines the effects of its knockdown on cellular biological characteristics. Using quantitative real-time PCR (qRT-PCR), lncBNIP3 expression was observed to be higher in muscle tissues compared to other tissues in both 1-day-old and 24-month-old Qinchuan cattle. Knockdown of lncBNIP3 expression upregulated the mRNA levels of proliferation-related genes, as confirmed by qRT-PCR, and subsequently enhanced cellular proliferation, as demonstrated through EdU assays, flow cytometry, and CCK-8 analysis. Transcriptomic sequencing of myoblasts revealed that differentially expressed genes (DEGs) were significantly enriched in pathways associated with DNA replication and the cell cycle. Shared DEGs were primarily enriched in the minichromosome maintenance (MCM) gene family. Additionally, qRT-PCR and transcriptomic sequencing results revealed that the knockdown of lncBNIP3 expression significantly upregulated the mRNA levels of MCM family genes, including MCM2 and MCM3. Fluorescence activity assays further showed that lncBNIP3 knockdown significantly enhanced the promoter activities of MCM2 and MCM3. These findings suggest that interference with lncBNIP3 expression promotes the proliferation of bovine myoblasts, potentially through transcriptional regulation of the MCM gene family. This study provides novel insights into the regulatory functions of lncRNAs in muscle development.

This paper identifies gene candidates differentially expressed in the porcine brain during sepsis, designed for eventual application in human clinical care for earlier detection of sepsis, as no known biomarkers currently exist. Sepsis associated encephalopathy (SAE) is characterized by dysregulated molecular pathways of the immune response impinging upon normal central nervous system (CNS) function and ultimately resulting in lasting cognitive and behavioral impairments. This study seeks to identify gene candidates that exhibit altered transcriptional expression during sepsis. Twelve Yorkshire pigs (n = 6 for saline control and lipopolysaccharide group) were utilized. LPS injection rate was 0.5-0.75 mL/kg resulting in death within 5-10 h. Brain tissue was collected and analyzed via bulk RNA-seq, and corresponding computational genomic analysis. Multiple genes demonstrated significant differential expression in the early septic brain, correlating with endothelial cell disruption, immune/inflammatory alterations, and potential alterations in microglia. Gene candidates downregulated include: OCLN, SLC19A3, and SLC52A3. Genes upregulated include: ICAM1, IRF1, CXCL10, and ZFP36. Specific gene candidates were identified as early changes in the septic brain that could be targets to prevent long-term cognitive and behavioral changes seen in sepsis survivors and establish a baseline diagnostic panel to interrogate in animal models with the goal of advancing treatments for human patients who experience sepsis.