Search Results (552)

Ankylosing spondylitis (AS) is a chronic inflammatory disease strongly associated with human leukocyte antigen B27 (HLA-B27). However, the incomplete penetrance of HLA-B27 suggests that additional molecular mechanisms contribute to AS pathogenesis. Circular RNAs (circRNAs) have emerged as important regulators of immune responses, but their roles in AS pathogenesis remain incompletely understood. In this study, circRNA expression profiles were examined by high-throughput RNA sequencing and selected circRNAs were validated by quantitative RT-PCR in T cells from AS patients and healthy controls. Among the validated circRNAs, circRNPS1 was significantly up-regulated in T cells from AS patients. Overexpression of circRNPS1 in activated Jurkat cells increased IL-2, IL-17A, and interferon-γ expression and enhanced JAK2/STAT1 and MEK1/2-ERK signaling. RNA pull-down followed by proteomic analysis identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) that binds to the back-splicing junction region of circRNPS1. CircRNPS1 increased the stability of hnRNPK and VAV1, whereas hnRNPK knockdown attenuated circRNPS1-mediated MEK1/2-ERK activation and inflammatory cytokine expression. Furthermore, an antisense RNA fragment targeting the back-splicing junction region of circRNPS1 suppressed IL-2, IL-17A, and interferon-γ expression in activated circRNPS1-overexpressing Jurkat cells and T cells from AS patients. Disrupting the interaction between circRNPS1 and hnRNPK therefore warrants further investigation as a potential therapeutic strategy for AS. Full article

Ribonucleoprotein granules such as processing bodies (P-bodies) and stress granules (SGs) are membrane-less organelles that regulate mRNA metabolism through liquid–liquid phase separation. UBAP2L drives SG assembly and can bridge P-bodies with SGs, yet how it is mobilized between these compartments remains unclear. Here, using co-immunoprecipitation, GST pull-down, CRISPR-Cas9-mediated knockout, and immunofluorescence microscopy, we demonstrate that CCHCR1 directly binds UBAP2L and that this interaction is dynamically regulated by stress intensity. Under mild oxidative stress, CCHCR1 retains UBAP2L in P-bodies; as stress intensifies, this interaction weakens, permitting UBAP2L release for SG assembly. CCHCR1 deficiency aberrantly traps UBAP2L in P-bodies via enhanced DDX6 association, resulting in defective SG assembly, delayed maturation, and increased P-body–SG fusion. These findings establish CCHCR1 as a stress-responsive switch that controls UBAP2L partitioning between P-bodies and stress granules, thereby controlling the threshold and kinetics of SG biogenesis. Full article

Given the strong association between major histocompatibility complex (MHC) class I and psoriatic arthritis (PsA), and the role of the MHC in antigen presentation potentially driving immunopathology, we performed mass spectrometry-based immunopeptidome analysis to identify MHC class I-bound peptides in PsA. MHC class I expression on circulating immune cells was determined by flow cytometric analysis. MHC class I-bound peptides were isolated via immunoaffinity purification and identified by mass spectrometry in PsA patients and healthy controls. MHC class I expression was increased on circulating immune cells in PsA. MHC class I immunopeptidome analysis revealed a high prevalence of peptides of nine-amino-acid length originating from intracellular source proteins, typical for MHC class I antigen presentation. Analysis of the MHC class I immunopeptidome showed a greater relative abundance of glutamic acid at position 2 in nonamers from PsA patients, but not controls. This finding was further corroborated by an unsupervised clustering analysis showing five different clusters in healthy individuals and six in PsA, with one featuring higher abundance of glutamic acid at position 2. The glutamic acid-containing PEQLRKLFI peptide from the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was exclusively identified in PsA patients both via MHC class I immunopeptidome analysis and via PEPperMap epitope mapping. In PsA, MHC class I expression is increased on circulating immune cells, and the MHC class I immunopeptidome is perturbed, with disease-related skewing towards greater relative abundance of glutamic acid at position 2 in nonamers and presentation of a unique peptide motif from the putative autoantigen hnRNP A1. Full article

Splicing factors, as core determinants of splice-site selection and dynamic spliceosome assembly, play pivotal roles in stress responses. This review systematically categorizes splicing factors involved in plant abiotic stress responses according to their functions as major spliceosomal components, dividing them into small nuclear ribonucleoproteins (snRNPs) and associated components, spliceosome assembly and disassembly factors, splicing regulatory factors, and proteins related to non-canonical RNA splicing. On this basis, we summarize their regulatory mechanisms of these factors under salt, drought, abscisic acid (ABA) signaling, temperature, and oxidative stresses. Through analyses across multiple species—including Arabidopsis thaliana, rice, maize, soybean, and wheat—we reveal both the evolutionary conservation and species-specific divergence of splicing-factor-mediated regulation. Currently, a large amount of research is still mainly at the transcriptome analysis or single phenotype validation stages, lacking in-depth analysis of direct targets, splicing isomer functions, and molecular mechanisms. Furthermore, current research is heavily concentrated on Arabidopsis, with relatively insufficient functional validation and breeding applications in crops such as maize and wheat. Despite substantial progress, several bottlenecks remain for translational applications in breeding, such as functional redundancy among splicing factor family members, growth penalties associated with overexpression, and tissue-specific and developmental-stage-dependent effects. To address these challenges, we discuss promising strategies, including CRISPR/Cas9-mediated splice-site editing, the use of inducible or tissue-specific promoters, and targeted modulation of upstream kinases, although extensive field trials and rigorous evaluations remain necessary. Collectively, this review provides a theoretical framework for understanding the roles of splicing factors in RNA-level regulation of plant stress adaptation and highlights their potential for breeding improvement. Full article

To investigate the effects of mulberry leaf extract (MLE) on the growth performance, organ indices, and flesh quality of grass carp (Ctenopharyngodon idella), a basal diet (Control, Crude protein 30.25%, Crude lipid 7.23%) and three MLE-supplemented diets containing 1%, 2%, and 4% MLE (MLE1%, MLE2%, MLE4%) were formulated. A total of 160 grass carp (259.7 ± 1.1 g) were randomly allocated into 16 cages (1 m × 1 m × 1.2 m), with 10 fish per cage and 4 replicate cages per treatment group. Throughout the 8-week feeding trial, juvenile grass carp were fed three times daily (08:00, 12:00, and 17:00) at a daily feeding rate of 1.5–2.0% body weight. At the end of the trial, growth performance was assessed. Additionally, four fish were randomly sampled from each cage to determine the organ indices, flesh quality parameters, and gene expression levels. In the results, the final average body weight of all groups ranged from 909.00 to 942.97 g, and all the groups exhibited no significant difference in growth performance (p > 0.05). MLE-supplemented groups had significantly decreased visceral somatic index and hepatic somatic index (p < 0.05). In terms of flesh quality, all MLE-supplemented groups increased the flesh shear force, springiness, whiteness, and lightness (p < 0.05). Compared with the Control group, the MLE4% group had increased flesh hardness, gumminess, and chewiness, from 2899.52 g, 1310.62, and 516.59 to 4122.99 g, 1958.48, and 887.76, respectively (p < 0.05). MLE significantly decreased the 48 h thawing loss (MLE2%), 96 h thawing loss (MLE1%, MLE2%, MLE4%), and flesh crude lipid content (MLE2%, MLE4%) (p < 0.05). In terms of collagen metabolism, compared with the Control group, MLE significantly increased the flesh collagen content (MLE2% and MLE4%) (p < 0.05), upregulated the expression level of La ribonucleoprotein 6 (MLE4%) and tissue inhibitor of metalloproteinase 1 (MLE4%). Matrix metallopeptidase 2 was significantly downregulated in all MLE-supplemented groups (p < 0.05). In terms of myofiber development, compared with the Control group, the myofiber density was higher, and the myofiber diameter was lower in all MLE-supplemented groups (p < 0.05). MLE significantly upregulated the expression level of mammalian target of rapamycin (MLE4%), musculoskeletal embryonic nuclear protein 1 (MLE4%), myogenic differentiation 1 (MLE2%, MLE4%), and myogenic factor 5 (MLE1%, MLE2%, MLE4%) (p < 0.05). Myotubularin-related protein 8 was significantly downregulated in all MLE–supplemented groups (p < 0.05). In conclusion, dietary supplementation with 2–4% MLE improves the flesh textural properties, chroma and water-holding capacity of grass carp. MLE improves the flesh quality of grass carp by enhancing collagen deposition and myofiber development. Full article

Influenza A virus (IAV) remains a major threat to global public health because of its capacity for antigenic drift, reassortment, zoonotic transmission, and pandemic emergence. Viral transcription and genome replication are carried out by the influenza virus RNA-dependent RNA polymerase (FluPol), a heterotrimeric complex composed of polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and polymerase acidic protein (PA), which functions together with nucleoprotein (NP) within viral ribonucleoprotein complexes (vRNPs). FluPol activity is regulated not only by viral determinants and host cofactors but also by diverse post-translational modifications. Among these, ubiquitination has emerged as a particularly versatile regulatory mechanism because it can control protein stability, polymerase assembly, subunit interactions, conformational dynamics, NP–RNA interactions, and innate immune signaling. Depending on the modified substrate, ubiquitin linkage type, acceptor residue, and responsible E3 ligase or deubiquitinase, ubiquitination may either restrict IAV replication or be exploited by the virus to enhance polymerase function and vRNP activity. This review summarizes recent advances in ubiquitination-mediated regulation of FluPol and NP, focusing on the responsible E3 ubiquitin ligases, deubiquitinases, ubiquitination sites, ubiquitin-chain types, and host restriction mechanisms. We further discuss the crosstalk between ubiquitination and other post-translational modifications, highlight unresolved mechanistic questions, and evaluate the therapeutic potential and challenges of targeting ubiquitin-dependent pathways for antiviral intervention. Collectively, this review provides a conceptual framework for understanding how ubiquitination shapes IAV replication and identifies E3 ligases and DUBs as potential targets for host-directed antiviral strategies. Full article

Circular RNAs (circRNAs) have recently emerged as a class of abundant and remarkably stable non-coding RNAs preferentially enriched in the nervous system. In neurons, the fine-tuned spatial regulation of gene expression is critical for proper synaptic function; accordingly, several studies have demonstrated that circRNAs exhibit highly compartmentalized localization, specifically within dendrites, axons, and synapses. These spatial localization properties imply the presence of active transport mechanisms, which control the intracellular trafficking of circRNAs. This review highlights the current understanding of circRNA transport in neurons, focusing on the molecular machinery driving synaptic enrichment. We explore the potential role of ribonucleoprotein-based transport as a primary mechanism driving circRNA localization and examine how such spatial distribution influences synaptic plasticity and post-transcriptional gene regulation. Finally, we discuss the clinical implications of these processes, exploring the link between dysregulated RNA transport and the development of neuronal abnormalities. Full article

The fragile X premutation (FXpm) is a relatively common condition caused by an expansion of 55–200 cytosine–guanine–guanine (CGG) repeats in the fragile X messenger ribonucleoprotein 1 (FMR1) gene. Previous studies have identified sensory processing challenges in children with the FXpm and reduced autonomic regulation in FXpm infants; no research has examined the relationship between autonomic nervous system (ANS) functioning or molecular variables and sensory responsiveness during infancy. This study examined parent-reported sensory responsiveness and its association with baseline respiratory sinus arrhythmia (RSA), interbeat interval (IBI), and CGG repeat length in 12-month-old infants with the FXpm (n = 35) and neurotypical (NT) controls (n = 55). Results indicated no significant differences in hyporesponsive or hyperresponsive sensory behaviors and no significant associations between baseline RSA or IBI and sensory responsiveness in either group. Within the FXpm group, however, greater CGG repeat length was associated with lower hyperresponsive sensory scores. These findings suggest that sensory processing differences may not be behaviorally evident at 12 months of age despite the presence of biological variability associated with the premutation. The study contributes to the emerging literature on early FXpm development and highlights the importance of examining genetic and physiological factors that may precede later-emerging behavioral phenotypes. Full article

We recently identified the U1 small nuclear ribonucleoprotein (U1-snRNP) antibodies in patients with Guillain–Barré syndrome (GBS), which is associated with the breakdown of the blood–nerve barrier (BNB). The objective of this study was to clarify the clinical significance of U1-snRNP antibodies in patients with GBS and its variants. We measured U1-snRNP antibodies using an enzyme-linked immunosorbent assay from the serum samples of patients with GBS (n = 106), Miller Fisher syndrome (MFS) (n = 24), and MFS/GBS overlap syndrome (MFS/GBS, n = 8). We compared the clinical characteristics of U1-snRNP positive and U1-snRNP negative GBS patients (n = 106). The cerebrospinal fluid (CSF)/serum albumin quotient (QALB)/QALBLIM [calculated as(age/15) + 4)] was calculated. The prevalence of U1-snRNP antibody positivity was 39% (41/106) in GBS, 0% (0/24) in MFS, and 50% (4/8) in MFS/GBS. The rate of U1-snRNP antibody positivity in the GBS and MFS/GBS groups was significantly higher than that in the MFS group. Levels of CSF proteins and QALB/QALBLIM were higher in U1-snRNP antibody-positive GBS than in U1-snRNP antibody-negative GBS among all GBS patients, as well as GBS patients with a preceding Campylobacter jejuni infection or AIDP. In conclusion, the U1-snRNP antibody-positive GBS group had a more severe breakdown of the BNB in U1-snRNP antibody-positive GBS patients than in U1-snRNP-negative GBS patients. The presence of U1-snRNP antibodies may be a clinical biomarker for predicting the progression of MFS to MFS/GBS. Full article

Influenza viruses are a major global health threat because of their recurring seasonal burden and continuing pandemic potential. Central to the viral life cycle is the viral ribonucleoprotein complex (vRNP), the functional unit of the segmented genome, in which each negative-sense RNA segment is encapsidated by oligomeric nucleoprotein (NP) and bound at its termini by the polymerase complex (FluPol). Recent advances in structural biology have revealed high-resolution structures of FluPol in distinct conformations, NP-RNA helical assemblies, and intact vRNP architectures, providing a structural framework for understanding vRNP assembly, polymerase conformational switching, and RNA synthesis in the RNP context. By contrast, current models for vRNP trafficking and selective genome packaging still rely largely on virological, biochemical, and cell biological evidence, with only limited structural resolution. In this review, we synthesize current knowledge of vRNP assembly, transcription, replication, intracellular trafficking, and selective genome packaging, and discuss the major unresolved questions in each area as well as their implications for antiviral development. Full article

Stress granules (SGs) are stress-induced ribonucleoprotein condensates assembled around untranslated mRNAs and RNA-binding proteins. G3BP1 is a central regulator of SG formation, yet the molecular events that initiate G3BP1-mediated condensation remain poorly understood. Current models propose that condensation is initiated by RNA–RNA interactions, G3BP1 self-association, or RNA-dependent assembly of G3BP1 into higher-order networks. To define the earliest steps of condensate formation, we employed high-speed atomic force microscopy (HS-AFM) to monitor G3BP1–RNA assembly at the nanometer scale. HS-AFM revealed that G3BP1 first associates with RNA to form discrete nascent assemblies that progressively recruit additional RNA and G3BP1 molecules. These assemblies subsequently grow into higher-order RNA–protein condensates through stepwise assembly. Together, these observations identify RNA-bound G3BP1 assemblies as the initiating structures of condensate formation and provide a framework for understanding the early stages of stress granule assembly. Full article

Soybean is a strategic crop for global protein and vegetable oil supply chains; however, genetic improvement remains constrained by genotype-dependent regeneration, variable transformation efficiency, and regulatory concerns regarding stable transgene integration. This review synthesizes emerging DNA-free and genotype-independent genome-editing frameworks for soybean, where genotype independence is defined as the ability to recover fertile, non-chimeric edited plants across elite germplasm. We critically examine the soybean genome-editing toolbox, including CRISPR-Cas9, Cas12a, multiplex editing systems, base editing, and prime editing, and discuss persistent bottlenecks associated with target selection, off-target assessment, editability, and plant recovery. Particular emphasis is placed on artificial intelligence (AI)-assisted approaches that integrate genomic, epigenomic, chromatin-accessibility, and multi-omics datasets to improve target prioritization, guide RNA design, off-target prediction, and locus- and genotype-specific editability assessment. We further evaluate DNA-free genome-editing technologies, including CRISPR-Cas ribonucleoproteins, transient RNA-based systems, and nanocarrier-mediated delivery platforms, highlighting their potential to generate non-integrative edits while reducing prolonged nuclease exposure. In addition, we discuss regeneration reprogramming strategies based on developmental regulators and morphogenic modules, including BBM-WUS, GRF-GIF, de novo meristem induction, and somatic embryogenesis, as enabling technologies for overcoming cultivar-dependent regeneration barriers. Importantly, this review proposes an integrated AI-to-field framework that connects target discovery, editability prediction, DNA-free editing, regeneration reprogramming, phenotypic validation, and breeding deployment into a unified soybean improvement pipeline. We further highlight emerging opportunities in multi-omics-guided target discovery, genotype-aware prediction models, regeneration-aware editing strategies, and closed-loop machine-learning systems that continuously improve editing decisions through experimental feedback. Collectively, these convergent innovations provide a practical foundation for accelerating the development of climate-resilient, nutritionally enhanced, and industry-ready soybean cultivars. Full article

The Yezo virus (YEZV) is a recently discovered tick-borne orthonairovirus with pathogenic potential, causing acute febrile illness in humans. Viral nucleoproteins (N) play a key role in genome packaging, replication, and modulation of host immune responses, making their structural characterization essential for understanding viral pathogenesis and developing targeted countermeasures. However, the absence of structural data for YEZV proteins significantly hinders these efforts. This study presents the first solution structure of the YEZV N domain 1 (D1). A highly purified, soluble, tag-free recombinant YEZV N D1 was produced from the native sequence of the clinical YEZV isolate. The native-state conformation was resolved through an integrated approach combining size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS), AlphaFold 3 structure prediction, and all-atom molecular dynamics simulations. The YEZV N D1 structure adopts a stable, predominantly α-helical globular fold that remains monomeric under near-physiological conditions. SEC-SAXS data show excellent agreement with computational models, revealing moderate conformational flexibility. The characterized recombinant YEZV N D1 and its first solution structure reported here providing essential insights into understanding of YEZV molecular architecture. These findings lay a foundation for rational serological assay development and structure-guided therapeutic design against this and other emerging orthonairoviruses. Full article

Splicing factor 3b1 (SF3B1), a component of U2 small nuclear ribonucleoprotein (U2 snRNP), has been known for its essential roles in pre-mRNA splicing and alternative splicing. Here we show that knocking down (KD) of SF3B1 broadly induced a significant reduction in mRNA expression in the genome. One of the genes whose expression is reduced by SF3B1 KD is methyl-transferase-like 3 (METTL3), a writer of N6-methyladenosine (m⁶A). We demonstrate that expression of both METTL3 mRNA and protein is affected by SF3B1 KD, which further decreases the m⁶A RNA expression level. m⁶A-seq indicates that SF3B1 KD affects m⁶A distribution within multiple genes in the genome. In addition, a high proportion of hypo-methylation events by SF3B1 KD (~70%) are overlapped in METTL3 KD cells, and a conserved m⁶A motif is observed in the hypo-methylated regions as in SF3B1 KD cells, suggesting the m⁶A decrease by SF3B1 is a direct effect of the reduced METTL3 expression. Furthermore, RT-qPCR using unlabeled RNA and 5-Bromouridine (BrU)-labeled nascent RNA and actinomycin D treatment demonstrates that transcription of METTL3 is significantly reduced but the mRNA decay rate is not altered, suggesting that METTL3 expression is altered at the transcription level. We further show that SF3B1 interacts with RNA polymerase (Pol) II in the RNA independent manner, further indicating the involvement of SF3B1 in transcription. Lastly, we demonstrate that the transcription inactive H3K27me3 on the METTL3 promoter was significantly increased whereas transcription active H3K4me3 was not changed by SF3B1 KD. Taken together, we conclude that reduced SF3B1 expression suppresses the transcription of METTL3 and inhibits m⁶A RNA expression. Full article

RNA-binding proteins (RBPs) are essential regulators of all aspects of RNA metabolism, including splicing, stability, localisation, translation, and degradation. Through their ability to recognise specific cis-elements in target transcripts, often via RNA-recognition motifs or other conserved domains, RBPs enable rapid cellular adaptation to stress and maintain proteostasis, particularly in post-mitotic tissues with limited transcriptional flexibility. Accumulating evidence positions RBPs as both modulators and drivers of the molecular hallmarks of ageing, including genomic instability, loss of proteostasis, mitochondrial dysfunction, cellular senescence, and chronic inflammation. This review synthesises peer-reviewed studies on the multifaceted roles of RNA-binding proteins in organismal ageing and age-related diseases. Key themes include the tissue- and age-dependent changes in expression of turnover and translation regulatory RBPs such as HuR (ELAVL1), AUF1 (HNRNPD), TIA-1, and tristetraprolin (ZFP36), which alter the stability of mRNAs encoding cell-cycle regulators, pro-inflammatory cytokines, and stress-response proteins. Systematic downregulation of core splicing factors, including PTBP1 and several heterogeneous nuclear ribonucleoproteins, drives widespread senescence-associated splicing alterations in pathways governing cell division, autophagy, DNA repair, and mitochondrial function, suggesting a causal contribution to the senescent phenotype. Prion-like RBPs such as TDP-43 and FUS exhibit age-dependent mislocalisation, nuclear depletion, and cytoplasmic aggregation, contributing to splicing defects, impaired RNA transport, and neurodegeneration in amyotrophic lateral sclerosis, frontotemporal dementia, and limbic-predominant age-related TDP-43 encephalopathy. Interactions between RBPs and non-coding RNAs, together with disrupted liquid–liquid phase separation dynamics, further exacerbate age-related decline. By integrating mechanistic studies from cellular and animal models with observations in human cohorts, this review underscores RBPs as central nodes linking multiple ageing hallmarks and highlights their potential as biomarkers and therapeutic targets to promote healthy ageing. Limitations of current models and priorities for future translational research are discussed. Full article