Search Results (510)

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants that continue to raise concern owing to their ability to accumulate in living organisms. In recent years, a growing body of research has shown that PFAS can exert their toxicity through disruption of both DNA integrity and epigenetic regulation. This includes changes in DNA methylation patterns, histone modifications, chromatin remodeling, and interference with DNA repair mechanisms. These molecular-level alterations can impair transcriptional regulation and cellular homeostasis, contributing to genomic instability and long-term biological dysfunction. In neural systems, PFAS exposure appears particularly concerning. It affects key regulators of neurodevelopment, such as BDNF, synaptic plasticity genes, and inflammatory mediators. Importantly, epigenetic dysregulation extends to non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which mediate post-transcriptional silencing and chromatin remodeling. Although direct evidence of transgenerational neurotoxicity is still emerging, animal studies provide compelling hints. Persistent changes in germline epigenetic profiles and transcriptomic alterations suggest that developmental reprogramming might be heritable by future generations. Additionally, PFAS modulate nuclear receptor signaling (e.g., PPARγ), further linking environmental cues to chromatin-level gene regulation. Altogether, these findings underscore a mechanistic framework in which PFAS disrupt neural development and cognitive function via conserved epigenetic and genotoxic mechanisms. Understanding how these upstream alterations affect long-term neurodevelopmental and neurobehavioral outcomes is critical for improving risk assessment and guiding future interventions. This review underscores the need for integrative research on PFAS-induced chromatin disruptions, particularly across developmental stages, and their potential to impact future generations. Full article

The RasGAP SH3 domain binding protein (G3BP) is a highly conserved family of proteins in eukaryotic organisms that coordinates signal transduction and post-transcriptional gene regulation and functions in the formation of stress granules. G3BPs have important roles in abiotic/biotic stresses in mammals, and recent research suggests that they have similar functions in higher plants. Brassica contains many important oilseeds, vegetables, and ornamental plants, but there are no reports on the G3BP family in Brassica species. In this study, we identified G3BP family genes from six species of the U’s triangle (B. rapa, B. oleracea, B. nigra, B. napus, B. juncea, and B. carinata) at the genome-wide level. We then analyzed their gene structure, protein motifs, gene duplication type, phylogeny, subcellular localization, SSR loci, and upstream miRNAs. Based on transcriptome data, we analyzed the expression patterns of B. napus G3BP (BnaG3BP) genes in various tissues/organs in response to Sclerotinia disease, blackleg disease, powdery mildew, dehydration, drought, heat, cold, and ABA treatments, and its involvement in seed traits including germination, α-linolenic acid content, oil content, and yellow seed. Several BnaG3BP DEGs might be regulated by BnaTT1. The qRT-PCR assay validated the inducibility of two cold-responsive BnaG3BP DEGs. This study will enrich the systematic understanding of Brassica G3BP family genes and lay a molecular basis for the application of BnaG3BP genes in stress tolerance, disease resistance, and quality improvement in rapeseed. Full article

Circular RNAs (circRNAs) are covalently closed RNA molecules generated through a non-canonical splicing event known as back-splicing. This particular class of non-coding RNAs has attracted growing interest due to its evolutionary conservation across eukaryotes, high expression in the central nervous system, and frequent dysregulation in various pathological conditions, including cancer. Traditionally, circRNAs have been characterised by their ability to function as microRNA (miRNA) and protein sponges. However, recent discoveries from multiple research groups have uncovered a novel and potentially transformative mechanism of action: the direct interaction of circRNAs with messenger RNAs (mRNAs) to regulate their fate. These interactions can influence mRNA stability and translation, revealing a new layer of post-transcriptional gene regulation. In this review, we present and analyse the latest evidence supporting the emerging role of circRNAs in diverse biological contexts. We highlight the growing body of research demonstrating circRNA-mRNA interactions as a functional regulatory mechanism and explore their involvement in key physiological and pathophysiological processes. Understanding this novel mechanism expands our knowledge of RNA-based regulation and opens new opportunities for therapeutic strategies targeting circRNA-mRNA networks in human disease. Full article

N6-methyladenosine (m6A) represents the most common and thoroughly investigated RNA modification and exerts essential functions in regulating gene expression through influencing the RNA stability, the translation efficiency, alternative splicing, and nuclear export processes. The rapid development of high-throughput sequencing approaches, including miCLIP and MeRIP-seq, has profoundly transformed epitranscriptomics research. These techniques facilitate the detailed transcriptome-wide profiling of m6A modifications, shedding light on their crucial roles in diverse biological pathways. This review comprehensively examines the identification, mechanisms of regulation, and functional consequences of m6A modifications. It emphasizes their critical roles in physiological contexts, encompassing immune function, neuronal development, and the differentiation of stem cells. Additionally, the review discusses the contributions of m6A dysregulation to pathological conditions, including cancer, neurodegenerative diseases, and disorders of metabolism. We also discuss the development and application of machine-learning algorithms for m6A site prediction, emphasizing the integration of sequence-based, structural, and evolutionary conservation features to enhance the predictive accuracy. Furthermore, the potential of applying the findings from m6A research in precision medicine and drug development is examined. By synthesizing the current knowledge and emerging trends, this review aims to provide a comprehensive understanding of m6A biology and its translational potential, offering new perspectives for future research and therapeutic innovation. Full article

Soybean (Glycine max L.) is grown worldwide to obtain edible oil, livestock feed, and biodiesel. However, drought and salt stress are becoming serious challenges to global soybean cultivation as they retard the growth of soybean plants and cause significant yield losses. Voltage-dependent anion-selective channel (VDAC) proteins are well-known for their role in drought and salt tolerance in crop plants. In this study, we identified 111 putative VDAC genes randomly distributed in genomes of 14 plant species, including cultivated soybean (Glycine max) and wild soybean (Glycine soja). The comparative phylogenetic studies classified these genes into six different clades and found the highest structural similarities among VDAC genes of G. max and G. soja. From the conserved domain database, porin-3 (PF01459) was found to be the conserved domain in all VDAC proteins. Furthermore, gene annotation studies revealed the role of GmaVDAC proteins in voltage-gated anion channel activity. These proteins were also found to interact with other proteins, especially mitochondrial receptors. A total of 103 miRNAs were predicted to target fifteen GmaVDAC genes. In G. max, these genes were found to be segmentally duplicated and randomly distributed on twelve chromosomes. Transcriptomic analysis revealed that the GmaVDAC18.2 gene showed overexpression in root nodules, whereas the GmaVDAC9.1, GmaVDAC18.1, and GmaVDAC18.2 genes showed overexpression under drought and salt stress conditions. Full article

The Colorado potato beetle (Leptinotarsa decemlineata, CPB) is a major pest in potato crops, notorious for its rapid dispersal and insecticide resistance, which are enabled by its robust elytra and flight-capable hindwings. The Miniature (Mi) gene, encoding a protein with a zona pellucida (ZP) domain, is involved in wing development and cuticle integrity, yet its functional role in beetles remains underexplored. In this study, we cloned and characterized the LdMi gene in the CPB and investigated its function using RNA interference (RNAi), morphological analyses, and spectroscopy. LdMi encodes a 146.35 kDa transmembrane protein with a conserved ZP domain, clusters with coleopteran homologs, and exhibits relative conservation across insect species. Expression profiling showed high LdMi transcript levels in the hindwings, the elytra, and the pupal stages. RNAi knockdown in fourth-instar larvae resulted in severe eclosion defects, including malformed wings and reduced adult weight. Scanning electron microscopy (SEM) revealed disrupted elytral patterns and deformed hindwing veins in knockdown individuals. Spectroscopic analyses using Fourier-transform infrared (FTIR) and Raman spectroscopy indicated a reduction in protein–chitin crosslinking and diminished hydrogen bonding, suggesting compromised cuticular integrity. These results highlight the essential role of LdMi in cuticle formation and the surface morphology of the elytra and hindwings, offering new insights into ZP domain proteins in insects. Full article

Liver fibrosis is a frequent pathological outcome of long-term liver diseases, arising from sustained damage to the liver. Two main types of liver damage can trigger fibrotic progression: hepatocellular injury, often caused by viral infections, alcohol, or metabolic disorders, and cholestatic injury, associated with impaired bile flow due to autoimmune or congenital conditions. Despite diverse etiologies, liver fibrosis exhibits conserved biological processes, including hepatocyte death, chronic inflammation, disruption of epithelial or endothelial barriers, and excessive deposition of extracellular matrix (ECM) components. These coordinated events reflect the complex interplay among parenchymal damage, immune activation, and fibrogenic signaling pathways. If unresolved, fibrosis may progress to cirrhosis, liver failure, or hepatocellular carcinoma. In the pursuit of non-invasive biomarkers for early detection and monitoring of fibrosis, extracellular vesicles (EVs) have garnered significant attention. Among the diverse cargoes within EVs, microRNAs (miRNAs) have emerged as particularly promising due to their stability, disease-specific expression patterns, and involvement in fibrogenic signaling. This review explores the role of EV-associated miRNAs in liver fibrosis, highlighting key candidates implicated in hepatocellular and cholestatic injury and their clinical potential as diagnostic and prognostic biomarkers, with special focus on MAFLD/MASH, primary sclerosing cholangitis, primary biliary cholangitis, and biliary atresia as representatives. Full article

Small non-coding microRNAs (miRNAs) play crucial roles in the degradation of the messenger RNAs (mRNAs) that are involved in various biological processes post-transcriptionally and translationally. Many plants, especially Musa spp. (plantains and bananas), which are important perennial herbs of the family Musaceae, experience significant yield loss due to abiotic stressors, yet only a few miRNAs involved in this response have been identified. This study employed in silico analyses of transcriptome shotgun assembly (TSA) and expressed sequence tag (EST) sequences to identify Musa miRNAs and their target genes. Leaf and root tissues from three Musa genomic groups (AAA, AAB, and ABB) under drought stress were analyzed using quantitative real-time PCR (qRT-PCR) to validate the expression of miRNAs. A total of 17 potential conserved miRNAs from 11 families were identified, with the minimal folding free energies (-kcal/mol) of precursors ranging from −136.00 to −55.70, as observed through RNA folding analysis. Six miRNAs (miR530-5p, miR528-5p, miR482a, miR397a, miR160h, and miR399a) showed distinct tissue-specific expression patterns in the roots and leaves across the three groups. A total of 59 target regulatory transcription factors and enzymes involved in stress response, growth, and metabolism were predicted. Of these, 11 targets were validated for miR530-5p, miR528-5p, miR482a, and miR397a, using qRT-PCR. These four stress-responsive miRNAs exhibited an inverse expression relationship with their target genes across two different tissues in Musa groups. This research provides insights into miRNA-mediated drought stress responsiveness in Musa spp., potentially benefiting future studies on gene regulation under drought stress. Full article

Circular RNAs (circRNAs) are single-stranded noncoding RNAs with a covalently closed loop structure. They are known for their stability, abundance, and highly conserved nature. Their expression is often specific to tissues or developmental stages. They interact with microRNAs (miRNAs) and RNA-binding proteins (RBPs) and they undergo N⁶-methyladenosine (m⁶A) modifications, further affecting gene transcription and translation. Increasing evidence over the past decades has revealed that dysregulated circRNA expression is associated with various neurological disorders, particularly the glioma, one of the most malignant tumors with a poor prognosis. Due to the presence of the blood–brain barrier (BBB) and drug resistance, conventional therapeutic approaches have shown limited efficacy. Recently, increasing attention has been directed toward precisely targeted therapies, with circRNAs emerging as promising molecules for cancer treatment. Studies indicate that circRNAs play a key role in glioma proliferation and metastasis. Substantial evidence indicates that exosomes can package circRNAs and facilitate their transport across the BBB into brain tissue, highlighting the potential of circRNAs as therapeutic targets for glioma. This review summarizes circRNAs’ functional mechanisms, clinical application relevance, and current limitations. It offers future research directions in this evolving field, aiming to encourage further research on circRNAs’ therapeutic applications and contribute to the development of novel glioma-treatment strategies. Full article

Background: Aluminum (Al) toxicity severely limits Medicago sativa (alfalfa) production on acidic soils, resulting in major yield losses worldwide. The highly conserved miRNA156 (miR156) functions by downregulating at least 11 SQUAMOSA promoter-binding protein-like (SPL) transcription factors in alfalfa, including SPL13, but its role in Al stress remains unclear. This study aimed to investigate the miR156/SPL regulatory network’s function in alfalfa under Al stress. Methods: Gene expression analyses, histochemical staining, nutrient profiling, phenotypic assays, transcriptome profiling, and ChIP-seq were conducted on alfalfa plants with altered miR156 and SPL13 expression to assess their roles in the Al stress response. Results: Al stress induced SPL13 expression while repressing miR156 in the roots. Elevated miR156 intensified Al accumulation, lipid peroxidation, and plasma membrane damage, accompanied by reduced leaf nitrogen, magnesium, sulfur, and phosphorus content. Phenotypically, increased SPL13 enhanced the root length and Al tolerance, whereas SPL13 silencing reduced tolerance. Transcriptome profiling of SPL13-silenced plants identified differentially expressed genes involved in the Al response, including aluminum-activated malate transporters and various transcription factors (GRAS, Myb-related, bHLH041, NAC, WRKY53, bZIP, and MADS-box). ChIP-seq revealed that SPL13 directly regulates genes encoding a protein kinase, cytochrome P450, and fasciclin-like arabinogalactan proteins. Conclusions: The MsmiR156/MsSPL13 network plays a crucial regulatory role in alfalfa’s response to Al toxicity. These findings provide novel genetic targets and foundational knowledge to advance molecular breeding for enhanced Al tolerance in alfalfa. Full article

Sjögren’s disease (SjD) is an autoimmune disease of exocrine tissues. Prior research has shown that ETS proto-oncogene 1 (ETS1), STAT1, and IL33 may contribute to the disease’s pathology. However, the regulatory mechanisms of these genes remain poorly characterized. Our objective was to explore the mechanisms of SjD pathology and to identify dysfunctional regulators of these genes by immunostimulation of SjD and sicca relevant cell lines. We used immortalized salivary gland epithelial cell lines (iSGECs) from Sjögren’s disease (pSS1) and sicca (nSS2) patients, previously developed in our lab, and control cell line A253 to dose with immunostimulants IFN-γ or poly(I:C) (0 to 1000 ng/mL and 0 to 1000 µg/mL, respectively) over a 72 h time course. Gene expression was determined using qRT-PCR delta-delta-CT method based on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for mRNA and U6 small nuclear RNA 1 (U6) for miRNA, using normalized relative fold changes 48 h post-immunostimulation. Protein expression was quantified 72 h post-stimulation by Western blotting. Reference-based RNA-seq of immunostimulated pSS1 and nSS2 cells was performed to characterize the reactome of genes conserved across all used doses. The expression of ETS1 and STAT1 protein was upregulated (p < 0.05) in IFN-γ-treated pSS1 and nSS2, as compared to A253 cells. IFN-γ-treated nSS2 cell showed significant IL33 upregulation. Also, IL33 had a correlated (p < 0.01) U-shaped response for low-mid-range doses for IFN-γ- and poly(I:C)-treated pSS1 cells. RNA-seq showed 175 conserved differentially expressed (DE) genes between nSS2 and pSS1 immunostimulated cells. Of these, 44 were shown to interact and 39 were more abundant (p < 0.05) in pSS1 cells. Western blotting demonstrated nSS2 cells expressing ETS1 uniformly across treatments compared to pSS1 cells, despite similar mRNA abundance. miR-145b and miR-193b were significantly under-expressed in IFN-γ-treated nSS2 cells compared to pSS1 cells (p < 0.01). ETS1 and IL33 showed disproportionate mRNA and protein abundances between immunostimulated Sjögren’s disease-derived (pSS1), and sicca-derived (nSS2) cell lines. Such differences could be explained by higher levels of miR-145b and miR-193b present in pSS1 cells. Also, RNA-seq results suggested an increased sensitivity of pSS1 cells to immunostimulation. These results reflect current pathobiology aspects, confirming the relevance of immortalized salivary gland epithelial cell lines. Full article

Berberis kaschgarica Rupr.-derived exosome-like nanovesicles (BELNs), a type of plant-derived extracellular vesicle, consist of proteins, lipids, and nucleic acids. In this research, we employed differential centrifugation and ultracentrifugation techniques to isolate and purify BELNs. Subsequently, we conducted a comprehensive multi-omics analysis to systematically determine their physicochemical properties. Experiments were conducted in vitro with Human Umbilical Vein Endothelial Cells (HUVECs) to verify the therapeutic impact of BELNSs on atherosclerosis. The isolated BELNs exhibited a distinctive teacup-shaped exosome morphology. The extraction yield was approximately 2.1 × 10¹³ particles per milliliter, and the average particle size was measured to be 179.1 nm. These nanovesicles were lipid-rich. The protein content predominantly comprised cytoplasmic proteins. In-depth analysis revealed the presence of five highly conserved plant microRNAs: miR166, miR156, miR399, miR171, and miR395. These miRNAs are involved in regulating plant growth and responses to both biotic and abiotic stresses. Functional assays demonstrated that Berberis kaschgarica Rupr.-derived exosome-like nanovesicles substantially decreased the lipid deposition in HUVECs that was triggered by Palmitic Acid (PA). This research establishes the inaugural utilization of multi-omics platforms to systematically elucidate the bioactivity profile of BELNs from Berberis kaschgarica Rupr., thereby laying the groundwork for advancing its therapeutic potential. Full article

MicroRNAs (miRNAs) are key post-transcriptional regulators involved in a wide range of biological processes in insects, yet little is known about their roles in stingless bees. Here, we present the first characterization of miRNAs in Melipona quadrifasciata using small RNAs (sRNAs) deep sequencing. A total of 193 high-confidence mature miRNAs were identified, including 106 M. quadrifasciata-exclusive sequences. Expression profiling revealed that mqu-miR-1 and mqu-miR-276 together accounted for over 70% of all miRNA reads, suggesting their central roles in development and reproduction. Comparative analyses showed a higher conservation of M. quadrifasciata miRNAs with other Hymenopterans, especially Apis mellifera and Bombus spp. Putative target genes were predicted using a consensus approach, and functional annotation indicated their involvement in diverse biological regulatory pathways. This work represents the first comprehensive identification of the miRNA repertoire in stingless bees using sRNAs and provides a valuable foundation for understanding miRNA-mediated gene regulation in this ecologically and economically important pollinator. Full article

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by inhibiting or degrading messenger RNAs (mRNAs). In ticks, salivary miRNAs are proposed to play key roles in modulating host–vector interactions during blood feeding. Previously, we identified salivary miRNAs in Ornithodoros moubata and Ornithodoros erraticus, major vectors of African swine fever and tick-borne human relapsing fever. In this study, we investigated the regulatory roles of salivary miRNAs in tick biology. Salivary miRNA datasets were re-analysed to identify conserved miRNAs, and putative target genes were predicted using the sialotranscriptomes of both species. In silico predictions were validated through experimental inhibition of specific miRNAs using antagomirs. Knockdown of miR-375 and miR-1 significantly reduced blood intake, oviposition, and fertility, indicating their involvement in feeding and reproductive processes. Silencing miR-252b in O. moubata led to increased mortality, suggesting a critical role in survival. Notably, Metis1 was identified as a likely target of miR-252b, and its dysregulation may underlie the observed lethality in miR-252b-silenced ticks. These findings highlight the functional relevance of salivary miRNAs in tick physiology and host interaction, offering new perspectives for the development of innovative tick control strategies. Full article

Soybean (Glycine max (L.) Merr.) is a critical crop in China, serving as a primary source of food, oil, and animal feed. Drought stress significantly impacts soybean growth and yield. MicroRNAs (miRNAs) play crucial roles in plant drought responses. The miR164 family is highly conserved across plant species and has been shown to participate in drought responses in a range of plants, yet the function of miR164 in soybean remains unclear. In this study, we identified GmNAC35 as a direct target of miR164 through published degradome sequencing data and 5′ RLM-RACE assays. Under drought stress, miR164 members (e.g., MIR164a, MIR164f, and MIR164k) rapidly down-regulated, reaching their lowest expression at 2 h and returning to basal levels within 6 h. Conversely, GmNAC35 showed an inverse pattern, indicating negative regulation by miR164. Overexpression of GmNAC35 enhanced drought tolerance in transgenic soybean plants, as evidenced by higher survival rates and reduced water loss. Transcriptomic analysis revealed that GmNAC35 modulates stress-responsive pathways, including ABA signaling and phenylpropanoid biosynthesis. Our findings indicate that miR164 negatively regulates GmNAC35, a positive regulator of drought tolerance. This enhances our understanding of the molecular mechanisms of drought tolerance in soybean and may inform strategies for breeding drought-resistant varieties. Full article