Search Results (526)

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

Target of rapamycin (TOR) is a conserved protein kinase that integrates nutrient and energy signals to control growth and metabolism, yet its proteome-level impact in microalgae remains poorly understood. Here, we conducted quantitative proteomics analysis of the unicellular red alga Cyanidioschyzon merolae under rapamycin-induced TOR inactivation to characterize global changes in protein abundance. TOR inhibition triggered widespread metabolic remodeling, including coordinated shifts in carbon and nitrogen allocation, and pronounced changes in protein synthesis, photosynthesis, and energy metabolism. Specifically, proteins associated with ribosome biogenesis and ribosomal subunits declined broadly, indicating impaired translation, alongside pronounced reductions in photosynthetic components, including PSI/PSII subunits and chlorophyll biosynthesis enzymes. In contrast, triacylglycerol (TAG) biosynthesis and starch metabolism were enhanced, indicating a shift towards carbon storage. Notably, a diacylglycerol acyltransferase (DGAT; CMQ199C) and a UDP-glucose pyrophosphorylase (UGP; CMS159C) were strongly induced (2.02-fold and 3.48-fold, respectively), identifying them as candidate targets for enhancing TAG and starch accumulation. Proteins associated with nitrogen assimilation were also upregulated, supporting TOR-dependent regulation of nitrogen metabolism at the protein level. Together, these results indicate that TOR orchestrates proteome-level reprogramming in C. merolae, coordinating growth, energy production, and carbon storage across interconnected metabolic pathways. Full article

Background: Skeletal muscle hypertrophy has traditionally been attributed to transient spikes in translational efficiency governed by the mTORC1 signaling cascade. However, contemporary molecular evidence reveals that sustained macroscopic growth is strongly associated with the physical expansion of the translational machinery itself. The activation of RNA Polymerase I and the subsequent synthesis of new ribosomes represent a critical biological correlate for long-term protein accretion. Objective: This comprehensive review critically examines ribosome biogenesis as the primary structural bottleneck shaping human skeletal muscle adaptation, differentiating acute signaling efficiency from chronic translational capacity. Synthesis: We dissect the molecular orchestration of nucleolar expansion and critically address the pervasive methodological pitfalls plaguing the current literature. Specifically, we highlight the moving denominator paradox, demonstrating how flawed bulk RNA normalization strategies systematically underestimate true ribosomal accretion in actively growing tissue. By synthesizing in vivo human evidence, we delineate how age, concurrent training, and training volume modulate this structural capacity. We further establish the high-responder phenotype as a function of successful nucleolar adaptation. Finally, we explore advanced molecular frontiers, including epigenetic chromatin remodeling, ribosomal heterogeneity as an emerging frontier, non-coding RNA regulation, and nuclear mechanotransduction via the YAP/TAZ axis. Conclusions: Acute anabolic signaling is merely permissive. Permanent hypertrophic adaptation fundamentally relies on overcoming the translational capacity bottleneck. Shifting the scientific and applied focus toward the architectural expansion of the nucleolus will fundamentally redefine practical hypertrophy programming and clinical interventions for sarcopenia. Full article

Junmu No.1 is a commercially important Chinese pig breed, yet stable in vitro models for investigating its muscle development mechanisms and genetic regulation remain lacking; this study aimed to establish an immortalized porcine satellite cell line from Junmu No.1 pigs to address this gap. Primary porcine satellite cells (PSCs) were isolated from a 2-day-old Junmu No.1 piglet and immortalized via lentiviral transduction using the pHAGE-EF1α-eGFP-SV40LT-BleoR vector. The resulting cell line (imPSC-JM) was characterized for morphology, satellite cell marker expression, karyotype stability, myogenic differentiation capacity, and long-term proliferative potential, and RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) was performed to assess transcriptomic fidelity relative to primary PSCs. The imPSC-JM line retained characteristic spindle-shaped satellite cell morphology, consistently expressed PAX7, maintained a normal diploid karyotype (2n = 38, XY), and showed stable SV40 large T antigen expression, enabling sustained proliferation exceeding 100 cumulative population doublings while preserving myogenic differentiation and the formation of multinucleated myotubes expressing Desmin, MYHC, and DMD. Transcriptomic profiles were highly concordant with primary PSCs (Pearson r ≥ 0.95; R² = 0.9188; 83.8% of expressed genes unchanged), with key satellite-cell and myogenic regulator genes (PAX7, MYOD1, MYF5, MYOG, MYF6) unaltered, while GSEA revealed upregulation of autophagy and inflammatory signaling and downregulation of ribosome biogenesis. The imPSC-JM line thus provides a reliable experimental platform with high transcriptomic fidelity for studying muscle development and genetic regulation in Junmu No.1 pigs. Full article

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants associated with neurodevelopmental and neurodegenerative disorders. PCB 118 is one of the most abundant congeners and exerts neurotoxic effects, yet the molecular mechanisms underlying its impact on human neurons remain poorly understood. We investigated the molecular response of retinoic acid-differentiated, neuron-like SH-SY5Y cells exposed to 5 µM PCB 118 for 24 h, a concentration that did not affect cell viability. RNA sequencing identified 1239 differentially expressed genes. Functional enrichment and protein-protein interaction analyses identified upregulation of histone and chromatin structural genes, indicative of substantial chromatin remodeling. In parallel, a significant downregulation of genes involved in ribosome biogenesis and rRNA processing was observed, potentially indicating impairment of the protein synthesis machinery. These transcriptional changes point to a coordinated reprogramming of nuclear architecture and translational machinery, potentially compromising neuronal homeostasis. The modulation of proteostasis-related pathways further supports a mechanistic link between PCB 118 exposure and neuronal dysfunction. Our results provide a comprehensive transcriptional framework connecting PCB 118 to chromatin-mediated gene regulation and suppression of ribosome biogenesis in human neuron-like cells. This study offers mechanistic insights into how environmental PCB exposure may contribute to neurotoxicity and highlights molecular pathways potentially implicated in the development of neurodegenerative disorders. Full article

Bombyx batryticatus is a traditional Chinese medicinal material derived from Bombyx mori infected by Beauveria bassiana; however, its formation mechanism remains poorly understood. This study compared infection processes in silkworms by two B. bassiana strains with markedly different virulence (highly virulent ZY027 and ARSEF2860). Integrated transcriptomic and proteomic analyses were employed to uncover, for the first time, the molecular basis of B. batryticatus formation at the systems biology level. The results demonstrated significant weight variations in B. batryticatus derived from different fungal strains. ZY027-induced stiff silkworms exhibited higher wet and dry weights than those infected by ARSEF2860. Large-scale gene reprogramming occurred in silkworm hemolymph post-infection, involving marked activation of Toll/Imd immune signaling pathways, ribosome biogenesis, and endoplasmic reticulum stress responses. A notable “uncoupling” between transcriptomic and proteomic profiles was identified, highlighting the critical role of post-translational regulation in host responses. The two strains triggered distinct metabolic reprogramming patterns: ZY027 notably suppressed oxidative phosphorylation and activated detoxification mechanisms, whereas ARSEF2860 presented characteristics of “immune–metabolic optimization.” These findings suggest that B. batryticatus formation involves complex fungus–silkworm molecular interactions in hemolymph, and that fungal strain characteristics are associated with significant differences in host molecular responses and product biomass. The study provides a theoretical foundation and innovative guidance for selecting strains with high B. batryticatus production potential and developing novel entomopathogenic fungal resources. Full article

Dense granule protein 47 (GRA47) of Toxoplasma gondii, which localizes to the parasitophorous vacuole membrane (PVM) and the parasitophorous vacuole (PV), is critical for PVM integrity, nutrient permeability, and parasite virulence. However, the global transcriptional response to GRA47 loss remains unexplored. High-throughput RNA sequencing was performed to compare transcriptomic profiles of a GRA47 knockout strain (RHΔgra47) and its parental wild-type RH strain. Differentially expressed genes (DEGs) were identified and analyzed by Gene Ontology (GO) and KEGG enrichment, with selected DEGs validated by reverse transcription quantitative real-time PCR (RT-qPCR). A total of 285 DEGs were identified, comprising 218 upregulated and 67 downregulated genes. Upregulated DEGs were enriched in autophagy, mitophagy, ribosome biogenesis, and GPI anchor biosynthesis pathways, along with nutrient starvation response terms, which may suggest potential roles for the activation of stress response and compensatory metabolic programs. Downregulated DEGs were enriched in host cell entry, rhoptry components, membrane-related terms, and the Hedgehog signaling pathway, a pattern that could suggest a possible association with resource allocation strategy. This first transcriptomic analysis of GRA47 loss in T. gondii identifies transcriptional changes that point to a possible resource allocation strategy prioritizing parasite survival over proliferation and offers a foundational resource for investigating compensatory mechanisms and developing novel intervention strategies. This study reports transcriptional changes only; further experiments are needed to confirm protein-level effects and biological function. Full article

Leptobotia elongata, a rare freshwater fish endemic to China, frequently exhibits retarded ovarian development under artificial captivity, severely constraining large-scale reproduction. This study evaluated the effects of combined dietary supplementation with fish oil (FO), soybean phospholipids (PLs), and vitamin E (VE) on ovarian development through a 6-month feeding trial. Hematoxylin and eosin staining revealed that oocytes in the mixed lipid group (MIX: FO + PL + VE) advanced to developmental stage III, whereas oocytes in the control group (CON) were predominantly arrested at stages I–II. Transcriptomic analysis identified 1393 differentially expressed genes (651 upregulated, 742 downregulated). Upregulated genes were enriched in nucleolus- and nuclear pore-related cellular components and RNA-binding molecular functions, indicating enhanced ribosome biogenesis capacity. Downregulated genes were concentrated in DNA damage repair pathways and Mediator complex-mediated transcriptional regulation, suggesting alleviation of oxidative stress. Protein–protein interaction network analysis identified mphosph10, utp11, nat10, emg1, and ftsj3 as core hub genes. Additionally, 44 differentially expressed transcription factors were identified, with Forkhead (forkhead.38), GATA (gata.4), and MYB (myb.40) significantly upregulated, indicating activation of a pro-developmental transcriptional program. These findings provide a theoretical basis for precision lipid nutrition formulation in L. elongata fish diets. Full article

Argonaute (AGO) proteins are central components of RNA silencing. While OsAGO18 is a known defense factor in antiviral immunity, its involvement in basal development and its transcriptomic behavior during fungal stress remains to be fully elucidated. In this study, based on its specific dual-localization in chloroplasts and processing bodies (P-bodies), we investigated the pleiotropic effects of OsAGO18 through transcriptomic network analysis of rice responding to the blast fungus Magnaporthe oryzae B.C. Couch. Our analysis revealed that the OsAGO18-mediated co-expression network is highly correlated with ribosome biogenesis and cell wall organization. Notably, the analyzed datasets reveal that this growth-related network is significantly suppressed upon M. oryzae challenge, highlighting a transcriptomic shift in OsAGO18 during the growth-to-defense transition. Phenotypic evaluations demonstrated that OsAGO18 overexpression accelerates early seedling growth and primary root elongation by promoting endogenous indole-3-acetic acid (IAA) accumulation, whereas ago18 mutants maintain basal growth rates without significant IAA fluctuations, reflecting robust genetic compensation within the highly redundant AGO family. Mechanistically, our integrated analysis suggests that OsAGO18 acts as a putative molecular decoy to sequester miR396d, thereby relieving the repression of the Growth-Regulating Factor OsGRF6 and triggering downstream auxin-dependent cascades. Collectively, our findings highlight OsAGO18 as a pivotal regulator of early seedling development and characterize its transcriptomic responsiveness to biotic stress, providing a plausible molecular link between post-transcriptional RNA regulation and rice growth coordination. Full article

Oocyte maturation is a pivotal event in teleost reproduction that directly determines egg quality, fertilization success, and the developmental competence of early embryos. However, the transcriptional and post-transcriptional regulatory mechanisms operating within oocytes during maturation in marine teleosts remain poorly understood. In the present study, the orange-spotted grouper (Epinephelus coioides), an economically important marine aquaculture species, was used as a model. Oocytes at four distinct maturation stages were obtained by microscopically removing the surrounding follicular layers, followed by integrated mRNA-seq and miRNA-seq analyses to characterize the molecular regulatory landscape underlying oocyte maturation and hydration. The results showed that, as maturation progressed, oocyte diameter and wet weight increased significantly, accompanied by a marked decrease in Na⁺ content, a significant increase in K⁺ content, and the continuous accumulation of most free amino acids, indicating the gradual establishment of an osmotic basis favorable for oocyte hydration. Transcriptomic analysis further revealed extensive transcriptional remodeling during both the early and late phases of maturation. Differentially expressed genes were significantly enriched in pathways related to oocyte meiosis, cytokine signaling, lipid metabolism, DNA replication, cell cycle regulation, ribosome biogenesis, spliceosome function, oxidative phosphorylation, and mitochondrial activity, suggesting that oocyte maturation is a dynamic process characterized by a shift from basal growth maintenance to metabolic reprogramming, maternal transcript remodeling, and terminal maturation responses. miRNA profiling identified a large number of stage-specific differentially expressed miRNAs, including let-7d-5p, miR-22a-3p, and novel-miR-20/27/118, whose predicted target genes were mainly enriched in ribosome-related pathways, oxidative phosphorylation, DNA replication, transcriptional regulation, and signal transduction. Moreover, the miRNA–TF–mRNA regulatory network demonstrated that miRNAs may not only directly repress target genes, but also mediate hierarchical regulatory cascades through transcription factors, thereby coordinately participating in cell cycle progression, cytoskeletal remodeling, vesicular transport, and immune- and cell communication-related responses. Collectively, this study provides the first systematic temporal atlas of mRNA and miRNA regulation during oocyte maturation and hydration at the oocyte level in a marine teleost, thereby deepening our understanding of the molecular basis of meiotic resumption and egg quality formation, and offering valuable theoretical support for the optimization of artificial breeding and the identification of key molecular targets in grouper reproduction. Full article

Vairimorpha ceranae (formerly Nosema ceranae) is an obligate intracellular parasite that poses a major threat to the health of the honey bee. Circular RNAs (circRNAs) have been recognized as key regulators in gene expression and pathogen–host interactions. However, their expression patterns and regulatory roles in V. ceranae infection remain largely unexplored. In this study, we performed circRNA profiling in V. ceranae spores (NcCK) and the midguts of Apis mellifera ligustica workers at 7 d post inoculation (dpi) and 10 dpi (Nc7T and Nc10T) based on transcriptome sequencing, followed by in-depth investigation of the regulatory roles of differentially expressed circRNAs (DEcircRNAs). In total, 243 circRNAs were identified in V. ceranae, with lengths predominantly ranging from 201 to 400 nucleotides. Comparative analysis screened 70 and 192 DEcircRNAs in the NcCK vs. Nc7T and NcCK vs. Nc10T comparison groups, respectively, with a significant majority being downregulated. The parental genes of these DEcircRNAs were significantly enriched in fundamental cellular processes and critical pathways such as protein processing in the endoplasmic reticulum and ribosome biogenesis. Additionally, we constructed a competing endogenous RNA network, suggesting that DEcircRNAs could potentially interact with DEmiRNAs to modulate mRNAs associated with fungal proliferation-relevant signaling pathways like MAPK, PI3K–Akt, and cAMP. Moreover, numerous DEcircRNAs were predicted to contain internal ribosome entry site elements, indicative of their potential for protein coding. The back-splicing junctions and expression trends of selected DEcircRNAs were successfully validated by RT-PCR and qRT-PCR. Our data not only offer a valuable resource for future functional studies but also provide a basis for elucidating the circRNA-mediated mechanisms underlying microsporidian pathogenesis and host–pathogen interactions. Full article

Background/Objectives: CD138 (syndecan-1) is a cell-surface heparan sulfate proteoglycan involved in cell–matrix interactions and growth factor signaling, and it has been implicated in tumor progression. However, the clinical significance of compartment-specific CD138 expression in breast cancer remains unclear. In this study, we investigated the prognostic and transcriptomic features of compartment-specific CD138 expression in invasive breast cancer. Methods: We performed an integrated analysis of immunohistochemistry and RNA sequencing of 111 invasive ductal carcinoma specimens. Tumors were classified into four groups according to CD138 expression in the tumor and stromal compartments. Clinicopathological data and survival outcomes were obtained from medical records, and transcriptomic profiles were analyzed using RNA sequencing. Results: The tumor-positive/stroma-negative phenotype (Group 1) was associated with poorer recurrence-free survival than the other phenotypes. According to multivariable Cox regression analysis, Group 1 remained an independent prognostic factor after adjustment for age, lymph node status, and Ki-67 index (hazard ratio, 5.493; p = 0.0028). Group 1 was also associated with lymph node metastasis and HER2 expression. All brain metastases occurred in Group 1, although the number of events was low. Transcriptomic profiling identified the upregulation of small nucleolar RNAs in Group 1 tumors, with the enrichment of pathways related to ribosome biogenesis, RNA processing, and translational regulation. Conclusions: Compartment-specific CD138 expression identifies an aggressive breast cancer phenotype with distinct transcriptomic features. This phenotype may have prognostic value and warrants validation using larger, independent cohorts. Full article