Search Results (537)

Syringaldehyde is a major lignin-derived inhibitor in lignocellulosic hydrolysates that affects growth, metabolism, and ethanol fermentation in Saccharomyces cerevisiae; however, the mechanisms underlying its toxicity and cellular adaptation remain poorly understood. In this study, fermentation analysis, physiological characterization, and transcriptomic profiling were integrated to investigate the response of S. cerevisiae to syringaldehyde stress. Syringaldehyde inhibited yeast growth and ethanol fermentation in a concentration-dependent manner. At 1.4 g/L, it caused only a minor decrease in final optical density at 560 nm (OD₅₆₀) (2.35%) but markedly decreased ethanol production and total sugar fermentation efficiency (18.65% and 17.64%, respectively), accompanied by delayed early-stage sugar utilization. Physiological analyses demonstrated that syringaldehyde induced cell-envelope alterations and induced membrane lipid peroxidation, whereas intracellular glycerol accumulation occurred only after prolonged exposure, indicating a delayed adaptive response. Transcriptome analysis identified 496 differentially expressed genes, with repression of ribosome biogenesis and cofactor biosynthesis and activation of the pentose phosphate pathway and aromatic aldehyde detoxification. Notably, ADH7, GND2, and TKL2 were strongly induced, suggesting enhanced NADPH-dependent detoxification. Collectively, these findings demonstrate that syringaldehyde induces coordinated physiological stress responses and metabolic reprogramming, including alterations in cell-envelope integrity, oxidative imbalance, and changes in fermentation-associated pathways, providing mechanistic insights into yeast adaptation to lignin-derived aromatic aldehyde stress and identifying potential targets for engineering more robust industrial yeast strains. Full article

Using a three-factor orthogonal design, we investigated the transcriptomic and histological responses of triploid rainbow trout (Oncorhynchus mykiss) gills across three salinities (10, 20, and 30 ppt) over 60 days, with temperature and body size as background conditions. Results showed that 20 ppt was associated with extensive transcriptional reprogramming, with 3333 differentially expressed transcripts (DETs), whereas 30 ppt induced only 120 DETs; WGCNA further identified salinity-correlated modules involved in ion transport and ribosome biogenesis. Histological alterations remained within physiological ranges with no salinity-dependent severity gradient, as confirmed by semi-quantitative scoring. These findings demonstrate that triploid rainbow trout gills employ distinct molecular strategies at medium versus high salinity. Within the 10–30 ppt range examined, 20 ppt was the salinity at which transcriptional reprogramming was most active, suggesting that this intermediate salinity warrants further investigation as a potential acclimation stage. Full article

The facultative endosymbiont Serratia symbiotica significantly influences the ecological fitness of its aphid host. However, the molecular mechanisms by which Serratia affects the host’s symbiotic organ, the bacteriocyte, remain poorly understood. Here, we conducted a comparative transcriptomic analysis of bacteriocytes from Serratia− and Serratia+ pea aphid (Acyrthosiphon pisum) strains. Our analysis revealed that Serratia colonization extensively modulates gene expression within bacteriocytes. Key metabolic pathways were significantly altered: genes involved in ribosomal biogenesis and oxidative phosphorylation were upregulated, while those in fatty acid biosynthesis were downregulated. Furthermore, we observed a complex reshaping of the immune profile, characterized by a broad downregulation of immune recognition and signaling components alongside an upregulation of specific effector genes and antioxidant enzymes. These findings suggest that Serratia induces a state of enhanced anabolic capacity and energy production in bacteriocytes, coupled with strategic reallocation of resources and a finely tuned immune response that balances symbiont tolerance with control. Our RT-qPCR validation confirmed the RNA-seq results, further supporting these results. This study provides the first bacteriocyte-specific transcriptomic resource for the aphid–Serratia interaction system, offering novel insights into the molecular integration of a facultative symbiont into host physiology. Full article

While chemosymbiosis offers deep-sea bathymodioline mussels a critical metabolic advantage, this dependence makes them vulnerable when removed from their native environment, and their early post-recovery dynamics remain poorly resolved. We maintained adult Gigantidas haimaensis collected from the Haima cold seep at atmospheric pressure and sampled gill tissues at 0, 3 and 9 h after collection. Coupled 16S rRNA amplicon sequencing and RNA-Seq were used to follow changes in the gill microbiota, host transcription and descriptive temporal covariation. Methyloprofundus remained the dominant bacterial genus throughout the experiment, whereas Ca. Vesicomyosocius, the SUP05 cluster, and operational taxonomic units (OTUs) assigned to Vibrio and Pseudoalteromonas had higher relative abundances at 9 h in the descriptive analysis and exhibited positive temporal covariation. RNA-Seq showed a stronger transcriptional shift at 3 h than at 9 h. Stress-related genes, including HSP70, HSP105, Toll-like receptors, fibrinogen-related proteins, dual oxidase, thioredoxin-system genes, ferritin, taurine transporter and sulfide:quinone oxidoreductase, changed markedly, while energy-consuming ribosome biogenesis was suppressed to conserve energy under combined physical and nutritional stressors. The temporal patterns of Ca. Vesicomyosocius and other low-abundance bacterial signals coincided with broad host stress and immune and metabolic transcriptional changes; gene-level microbiome–transcriptome associations were exploratory and did not survive false-discovery-rate (FDR) correction. These results document rapid short-term transcriptional and microbiome changes after recovery, while their causal drivers and consequences require controlled validation. Full article

Pectic polysaccharides from tea residues represent a promising class of prebiotic dietary fibers. This study aimed to optimize the extraction of Oolong tea (Camellia sinensis ‘Foshou’) polysaccharides (FCTP), elucidate the structural alterations induced by ultrasonic degradation, and evaluate the consequent in vitro utilization using Lactobacillus salivarius BXP5. Enzyme-assisted extraction significantly improved the yield of FCTP to 11.10%, compared to 6.74% via conventional hot-water extraction. Ultrasonic treatment (120–240 W, 20–45 min) reduced the molecular weight (Mw) from 1079.9 kDa to 690.7–824.4 kDa, increased the uronic acid content, disrupted the triple-helix conformation, and transformed the polysaccharide into a looser and more water-accessible structure. Structural characterization by FTIR, methylation, and NMR further indicated that uFCTP remained an acidic pectic polysaccharide enriched in homogalacturonan (HG)-like domains. In vitro fermentation demonstrated that ultrasonically degraded FCTP (uFCTP) more effectively promoted BXP5 proliferation than native FCTP. Non-targeted metabolomics and proteomics revealed that uFCTP exerted more pronounced regulatory effects on nucleotide metabolism, carbon metabolism, and ribosomal biogenesis. Correlation analysis identified key metabolites (e.g., gallic acid, xanthosine monophosphate) tightly associated with differentially expressed proteins involved in carbohydrate utilization and cellular growth. These findings indicate that ultrasonic degradation is an effective physical modification strategy to improve utilization by L. salivarius BXP5 of tea-derived pectic polysaccharides by tailoring their molecular architecture for improved probiotic fermentation and metabolic cross-talk. Full article

The RNA exosome plays a critical role in surveilling nuclear mRNA biogenesis and regulating co-translational mRNA decay in the cytoplasm. Unlike canonical translation, repeat-associated non-AUG (RAN) translation of a GGGGCC hexanucleotide repeat expansion (HRE) within an intron of the C9orf72 locus leads to the synthesis of neurotoxic dipeptide-repeat (DPR) proteins, contributing to the pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis (C9-ALS/FTD). However, it remains unclear whether aberrant RAN translation is monitored and regulated co-translationally or how C9orf72 HRE (C9-HRE) mRNA is degraded during this process. Here, we demonstrate that RAN translation triggers the rapid decay of C9-HRE mRNA. During this process, the RNA exosome engages the translating ribosome-C9-HRE mRNA complex to mediate RAN translation-coupled mRNA decay. Moreover, overexpression of EXOSC3, a key subunit of the RNA exosome cap, promotes RAN translation-coupled decay of C9-HRE mRNA and suppresses DPR production. In iPSC-derived neurons, a reduction in EXOSC3 levels blocks C9-HRE mRNA decay in a translation-dependent manner, further confirming its role in RAN translation surveillance. These findings highlight the essential function of the RNA exosome, particularly EXOSC3, in mitigating RAN translation-associated toxicity and preventing pathological DPR production. This work provides insights into potential therapeutic strategies for C9-ALS/FTD and may have broader implications for other disorders involving RAN translation. Full article

The nucleolus has emerged as a dynamic and multifunctional subnuclear organelle that integrates ribosome biogenesis with cellular growth and stress signalling. Dysregulation of nucleolar function is increasingly recognised as a central driver of human disease, linking altered ribosome production and nucleolar surveillance pathways to cancer, ribosomopathies, premature ageing syndromes, neurodegeneration, and immune disorders. In this review, we integrate structural, molecular, and disease-level perspectives on nucleolar biology to define how ribosome biogenesis and nucleolar surveillance regulate cellular state across physiological and pathological contexts, positioning the nucleolus as an active regulator of cell function. We outline areas of convergence, identify key unresolved questions, and highlight therapeutic vulnerabilities that arise, including opportunities for small-molecule inhibitors and gene-based approaches. Full article

The yeast metabolic cycle (YMC) in Saccharomyces cerevisiae provides a tractable model for examining how mitochondrial respiration, redox timing, and metabolic phase shape transcriptome abundance and fidelity. Ribosomal-RNA-depleted whole-transcriptome RNA sequencing (WRS) and RNA-seq-derived mismatch analyses were performed across low-dissolved-oxygen (Low-DO)/high-respiration and high-dissolved-oxygen (High-DO)/lower-respiration phases. Among 1505 phase-differentially expressed genes, Low DO was enriched for ribosome biogenesis, rRNA processing, translation, sulfur metabolism, and protein synthesis, whereas High DO was enriched for oxidant detoxification, oxidoreductase activity, and redox-buffering-related pathways. Generalized linear mixed models identified a substitution-class-dependent Low-DO-associated RNA-seq mismatch response. The strongest mismatch-level increase occurred in the collapsed C > T/G > A-compatible class, whereas C > A/G > T did not increase. This pattern was not consistent with a simple single-lesion model and instead supported a mixed Low-DO-associated RNA-seq sequence-discordance landscape. Variant-rate modeling additionally detected T > C/A > G and T > A/A > T increases, indicating that multiple biological and technical processes may contribute to the observed spectrum. Recurrence analysis showed that most called variants were sample-specific, supporting a transient RNA-seq mismatch landscape rather than stable DNA mutation. These findings establish the YMC as a reductionist eukaryotic framework for studying how metabolic phase and redox state shape transcriptome fidelity. Full article

Objective: To investigate the clinical characteristics, inheritance patterns, and genotype–phenotype correlations of DHX37 variants in 46,XY disorders of sex development (DSD). Methods: We retrospectively reviewed 108 patients with 46,XY karyotype who underwent DSD evaluation and trio-based whole-exome sequencing (trio-WES) at our center between January 2021 and December 2025. Six probands with DHX37 variants and no concurrent pathogenic or likely pathogenic variants in other known DSD-associated genes were analyzed in detail. Clinical presentations, endocrine profiles, imaging findings, and pedigree data were collected. Variant segregation was confirmed by Sanger sequencing; variants were assessed using in silico prediction, conservation analysis, and structural modeling, and were classified according to ACMG/AMP guidelines. Results: The six probands exhibited marked phenotypic heterogeneity, with manifestations ranging from complete gonadal dysgenesis to mild testicular underdevelopment with gynecomastia. Six heterozygous DHX37 missense variants were identified across distinct functional domains: one in RecA1 [c.1000C>T (p.Arg334Trp)], four in RecA2 [c.1379T>C (p.Val460Ala), c.1432G>A (p.Gly478Arg), c.1730A>G (p.Asp577Gly), and c.1954G>A (p.Val652Ile)], and one in the linker region proximal to the HA2 domain [c.2180C>T (p.Thr727Met)]. Of these, p.Arg334Trp is an established pathogenic variant; p.Gly478Arg has been reported previously, albeit in the same patient included in the present study; and the remaining four were novel. According to ACMG/AMP guidelines, p.Arg334Trp was classified as pathogenic, and the remaining five as variants of uncertain significance. Conclusions: This study provides additional case evidence supporting the pathogenicity of p.Arg334Trp and expands the DHX37 variant spectrum. Computational and structural analyses suggest that p.Gly478Arg may underlie the testicular regression syndrome phenotype of the corresponding proband and that the four novel variants may be involved in testicular development. However, these genotype–phenotype correlations remain speculative; larger cohorts and in vitro functional assays are warranted to confirm these associations. Full article

Lactation traits are important indicators for evaluating the production performance of dairy cows and the economic efficiency of dairy production. Identifying potential regulatory genes is essential for elucidating the molecular mechanisms underlying lactation and facilitating molecular breeding. This study aimed to identify candidate genes and regulatory pathways potentially associated with lactation traits in dairy cows by integrating transcriptome expression profiles of primary bovine mammary epithelial cells (BMECs) from eight Holstein cows with lactation phenotypic data. A gene co-expression network was constructed using weighted gene co-expression network analysis (WGCNA). Co-expression modules associated with lactation traits were identified, and candidate genes were further screened by integrating gene significance, module membership, functional enrichment analysis, random forest analysis, gene-phenotype association analysis, single-gene gene set enrichment analysis (GSEA), ROC curve analysis, and tissue expression profiling. Four co-expression modules, namely MEdarkturquoise, MEsteelblue, MEbrown, and MEskyblue3, were significantly associated with lactation traits (p < 0.05). Genes in these modules were mainly enriched in biological processes and pathways related to ribosome biogenesis, protein translation, the cell cycle, oxidative phosphorylation, and the PI3K-Akt signaling pathway, which may be involved in lactation regulation. Through multi-strategy cross-screening, four candidate genes were ultimately identified. MDM2 was associated with daily milk yield (DYM), RPL37A with total milk solids (TMS), and SLC25A25 and CCNE2 with milk fat percentage (MFP) and fat-to-protein percentage ratio (FPP). Reverse transcription quantitative real-time PCR (RT-qPCR) validation showed that MDM2 and RPL37A were relatively highly expressed in mammary tissue, suggesting that they may be involved in lactation-related biological processes in dairy cows. These findings provide potential candidate regulators and theoretical support for further studies on the molecular mechanisms of lactation traits; however, their functional roles require further validation through in vitro and in vivo experiments. Full article

2,4-Dichlorophenoxyacetic acid (2,4-D), originally developed as a synthetic auxinic herbicide, is the most widely used chemical inducer of somatic embryogenesis (SE) in plants. Despite extensive use of 2,4-D in plant regeneration, the systems-level regulatory mechanisms connecting hormonal signaling, metabolic reprogramming, translational control, and embryogenic competence remain poorly resolved. Here, we hypothesize that TOR signaling functions as an integrative molecular hub coordinating transcriptional, metabolic, and developmental reprogramming during somatic embryogenesis induction. To investigate the molecular regulatory landscape associated with 2,4-D-induced SE, we performed a systems-level analysis integrating publicly available transcriptomic data from Arabidopsis thaliana with high-confidence protein–protein interaction (PPI) network analyses using STRING v12.0 (confidence score ≥ 0.900). Using a previously published transcriptomic dataset, we identified 1927 upregulated genes associated with SE induction, which were organized into 34 functional modules related to transcriptional regulation, translation metabolism, hormone signaling and cellular homeostasis. Within this interactome, TARGET OF RAPAMYCIN (TOR) kinase emerged as an integrative regulatory hub associated with multiple pathways involved in embryogenic reprogramming. Network analyses revealed three major TOR-associated regulatory axes: (1) the TOR–FKBP12–RPS6A axis, associated with ribosome biogenesis and translational regulation; (2) the TOR–CBP20 axis, connected with transcriptional reprogramming; SE master regulators (LEC1, LEC2, and FUS3); and lipid, sterol, brassinosteroid (BR), and auxin-associated pathways; and (3) the TOR–TAP46 axis, linked with one-carbon metabolism, nucleotide biosynthesis, DNA replication and repair, and genome-stability pathways. Additionally, the network contained 411 embryo-lethal (EMBL) genes distributed across multiple regulatory modules, reinforcing the biological relevance of the identified interactome and highlighting the importance of coordinated developmental, metabolic, and transcriptional regulation during embryogenesis induction. These findings support a systems-level TOR-associated regulatory framework involved in the integration of transcriptional, translational, metabolic, hormonal, and genome-maintenance pathways during embryogenesis. This interactome model provides a foundation for functional studies aimed at dissecting the molecular mechanisms underlying SE and identifying candidate targets to improve regeneration and biotechnological application and crop genetic engineering. Collectively, this study proposes a mechanistic framework in which TOR signaling integrates developmental, metabolic, translational, and genome-stability pathways to orchestrate embryogenic competence, providing candidate molecular targets for improving plant regeneration and genome engineering platforms. Full article

Climate change is expected to increase temperatures in agricultural producing regions, potentially affecting fruit development and quality. To date, the molecular responses of raspberry fruits to moderate warming under field conditions have not been explored. In this paper, raspberry plants (Rubus idaeus L. cv. Heritage) growing in two contrasting agroclimatic regions of Chile were exposed to a moderate increase in temperature during fruit development. Fruit phenotyping, histological analyses, and RNA sequencing were used to evaluate physiological and transcriptomic responses to warming. Elevated temperature increased fruit weight and fruit dimensions in both orchards and was associated with larger drupelet and cell areas, which was accompanied by reduced cell density. Moreover, transcriptomic analyses revealed marked differences in gene expression responses between raspberries fruits from different locations with only a small number of heat-responsive genes shared across locations. Nevertheless, the common enrichment of oxylipin-related processes was observed, suggesting a conserved response. In addition, a combined treatment model identified the enrichment of processes like ribosome biogenesis, RNA metabolism, cell cycle regulation, cytokinesis, and structural cellular remodeling. These transcriptional changes were consistent with the cellular phenotypes observed in heat-treated fruits. Overall, our results show that moderate warming promotes larger raspberry fruits through changes in cellular organization, while the underlying molecular responses are strongly influenced by agroclimatic context. Full article

Dysregulation of ribosome biogenesis is increasingly recognized as a hallmark of tumor malignancy, yet its prognostic implications in lung adenocarcinoma (LUAD) remain incompletely characterized. This study aimed to construct a ribosome biogenesis-related prognostic model for LUAD and explore its potential relevance to the tumor immune microenvironment. Single-cell and bulk RNA sequencing data were integrated to identify ribosome biogenesis-related genes (RBRGs), from which a prognostic risk score was established via Cox regression, LASSO regression, and multivariate Cox analyses and validated in two independent GEO cohorts. Associations between the risk score and tumor mutation burden, immune infiltration, and computationally inferred immunotherapy response were systematically evaluated. In vitro experiments were performed to characterize the biological function of RPS19BP1, a key gene in the model. A total of 262 RBRGs were identified, and the derived 14-gene risk score demonstrated prognostic value across three cohorts (TCGA: 1-, 2-, 3-year AUC = 73.08, 72.44, 72.20; GSE68571: 1-, 2-, 3-year AUC = 67.93, 73.24, 77.59; GSE8894: 1-, 2-, 3-year AUC = 75.56, 72.99, 71.77). The low-risk group exhibited a more immunocompetent tumor microenvironment, whereas the high-risk group was associated with an immunosuppressive phenotype. Knockdown of RPS19BP1 significantly attenuated the proliferation, migration, and invasion of LUAD cells. This multi-omics-derived prognostic model showed prognostic potential in retrospective LUAD cohorts, is associated with distinct immune infiltration patterns, and identifies RPS19BP1 as a pro-oncogenic regulator in LUAD. Full article

Across all kingdoms of life, ribosomes are indispensable molecular machines that translate genetic information into the proteome of living cells. The fundamental catalytic centers of the ribosome, constructed primarily from ribosomal RNA (rRNA), exhibit remarkable conservation between the major domains of life. The ribosome’s A-site deciphers the mRNA’s triplet code, while the P-site synthesizes the growing protein chain and the E-site provides exit for deacylated tRNA; a distinct tunnel facilitates nascent polypeptide export. While the conservation of ribosomal proteins is less pronounced between bacteria and eukaryotes, striking homology exists from simple eukaryotes to humans. Ribosomal proteins were traditionally viewed mainly as scaffolding agents, steering rRNA folding during ribosome biogenesis and maintaining structural stability during translation. However, since the early 2000s, advances in structural and functional ribosome analysis have ushered in a more nuanced paradigm: ribosomes are no longer considered uniform machines. Instead, an array of rRNA and ribosomal protein modifications generates a spectrum of ribosome populations capable of specialized translation. RiboScreen^TM technology leverages this regulatory potential of individual ribosomal proteins, enabling deliberate modulation of target protein output and representing a promising tool for correcting dysregulated protein expression involved in rare and common diseases. This review will first introduce relevant aspects of ribosome biology and then showcase the tools of this new technology. Finally, we report examples for the delivery of small molecules to target ribosomal proteins for tailored restoration of protein production levels in rare and prevalent diseases. Full article

Wilson–Turner syndrome (WTS) is an X-linked developmental disorder associated with variants in the LAS1L gene, which plays a role in ribosome biogenesis. We report a 6-year-and-5-month-old boy presenting with growth retardation, early developmental delay, and mild scoliosis. Exome sequencing analysis identified a novel hemizygous LAS1L frameshift variant, c.2082dup (p.Leu697ProfsTer59), inherited from his asymptomatic mother that was absent from population databases. Functional analysis in HEK-293T cells suggested reduced protein expression with a partial loss of function effect, while structural modeling indicated potential alteration of the C-terminal region. The patient lacked classical WTS features, including craniofacial dysmorphism, truncal obesity, hypogonadism, and neuromuscular involvement. This case expands the phenotypic spectrum of LAS1L-related disorders and highlights the consideration of LAS1L variants in children with unexplained growth failure, scoliosis, or developmental delay, even in the absence of classical WTS features. Full article