Molecular Genetics and Genomics最新文献

{"title":"The genome-wide analysis of the NAC gene family in Pseudoroegneria libanotica highlights the functions of PlNAC17/20 under abiotic stress conditions.","authors":"Xuejie Jia, Yongchun Li, Xingguang Zhai, Yumin Yang, Xunzhe Yang, Xia Wang, Yonghong Zhou, Haiqin Zhang","doi":"10.1007/s00438-026-02470-8","DOIUrl":"10.1007/s00438-026-02470-8","url":null,"abstract":"<p><p>Pseudoroegneria libanotica is a cool-season forage with high drought tolerance. NAC (NAM, ATAF and CUC) plays an important role in plant growth and development and adaptation to a variety of abiotic stresses. To date, no NAC gene family has been reported in Pse. libanotica. The primary objective of this study was to comprehensively characterize the NAC gene family and elucidate its functional involvement in drought stress responses. 217 NAC genes were identified in the Pse. libanotica genome and classified into 11 subfamilies based on phylogenetic analysis with Arabidopsis and rice NAC reference proteins. Collinearity analysis showed stronger syntenic conservation between Pse. libanotica and wheat than between Pse. libanotica and Arabidopsis. Duplication and Ka/Ks analyses suggested that dispersed duplication contributed mainly to PlNAC family expansion and that duplicated PlNAC genes were primarily under purifying selection. Physiological measurements confirmed progressive drought stress, and transcriptome analysis identified 14 drought-responsive PlNAC genes. Among them, PlNAC17 and PlNAC20 showed strong drought-responsive expression patterns. Structural and subcellular localization predictions supported their potential roles as NAC transcription factors. Co-expression analysis identified two LEA-like genes and one U-box domain-containing protein gene as PlNAC17-associated stress-responsive candidates. Yeast heterologous expression assays showed stress-dependent effects of PlNAC17 and PlNAC20 under different abiotic stresses. This study provides the first genome-wide analysis of the NAC gene family in Pse. libanotica and identifies PlNAC17 and PlNAC20 as candidate stress-responsive NAC genes. These findings provide valuable information for understanding NAC-mediated stress regulation and for future improvement of stress tolerance in Triticeae crops.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Professor Thomas Börner: the pioneer of molecular plant genetics in East Germany turns 80!","authors":"Christian Schmitz-Linneweber, Reimo Zoschke","doi":"10.1007/s00438-026-02498-w","DOIUrl":"10.1007/s00438-026-02498-w","url":null,"abstract":"","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulatory network of Salmonella biofilm formation: the role of CsgD on autoinducer-2 activity and expression of quorum-sensing-related genes in Salmonella Typhimurium.","authors":"Melih Aşan, Fatma Neslihan Özdemir, Nefise Akçelik","doi":"10.1007/s00438-026-02508-x","DOIUrl":"10.1007/s00438-026-02508-x","url":null,"abstract":"<p><p>Salmonella biofilms are mainly formed by cellulose and curli fimbriae under the control of CsgD. Biofilm regulation also involves small RNAs and LuxS-mediated AI-2 quorum sensing. This study aimed to investigate the relationship between CsgD and quorum-sensing regulation in Salmonella Typhimurium. By modulating csgD expression, the impact on the expression levels of MicA, CsrB, CsrC, and RyeE sRNAs-sRNAs implicated in QS-linked regulatory pathways-was assessed. Quantitative real-time PCR (qRT-PCR) analyses demonstrated that the expression of these sRNAs was increased following perturbation of CsgD levels. Furthermore, the influence of CsgD levels on AI-2 activity was evaluated, revealing that strains overexpressing csgD displayed a 277% increase in relative AI-2 activity compared with the wild-type strain. Additionally, the effects of csgD on the expression of lsrA, lsrK, and lsrR genes, which are part of the Lsr transport system for AI-2 uptake, were investigated. In the strain with elevated AI-2 activity, a marked increase in lsrK expression was observed. Conversely, loss of csgD resulted in the upregulation of lsrA, lsrK, and lsrR, while AI-2 activity remained largely unchanged. This pattern suggests that the inhibitory effect of LsrR on QS signaling may be counterbalanced by increased expression of lsrA and lsrK. Collectively, our findings indicate that changes in CsgD levels are associated with shifts in QS-linked sRNA expression and AI-2 signaling dynamics. In addition, deletion of csgD resulted in reduced biofilm-associated phenotypes, including curli- and cellulose-related traits and biofilm biomass, whereas partial restoration of these phenotypes was observed in the complemented strain. Results suggest that CsgD may act as an integrative regulatory node linking transcriptional control of biofilm formation with quorum-sensing signaling pathways in Salmonella.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-genome analysis reveals the triangle mechanisms of antibiotic resistance, pathogenicity, and biofilm formation in Enterococcus faecalis.","authors":"Eswar Rao Tatta, Ranjith Kumavath","doi":"10.1007/s00438-026-02504-1","DOIUrl":"10.1007/s00438-026-02504-1","url":null,"abstract":"<p><p>The bacterial genus Enterococcus is typically nonpathogenic and a commensal that lives symbiotically with humans. However, the transition from commensal to opportunistic pathogenic is a complex, multi-step process driven by environmental adaptation. The study focused on 214 Enterococcus faecalis genome sequences, selected from various environments and organisms, including humans and animals, and targeted genes associated with biofilm formation, antibiotic resistance, and quorum sensing. KEGG pathway analysis identified 36 potential drug targets, comprising n = 15 non-enzymatic and n = 21 enzymatic targets, primarily located in the cytoplasm, including four surface proteins and seven pharmacological targets. The study also revealed resistance-conferring genes, including ABC transporters, major facilitator superfamily (MFS) proteins, and antibiotic efflux pumps, which mediate resistance to glycopeptides, quinolones, aminoglycosides, and tetracyclines. In this pangenome study, critical insights into the development of multidrug resistance in nosocomial pathogens are provided. Insights into the outcomes could enlighten novel drug designs and strategies to combat infections in both clinical and environmental settings.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZNF143 suppresses mitophagy to drive MASLD progression by regulating SMURF1/TRPV1 axis.","authors":"Mei Long, Kewei Tan, Yujie Dong","doi":"10.1007/s00438-026-02501-4","DOIUrl":"10.1007/s00438-026-02501-4","url":null,"abstract":"<p><p>Metabolically dysfunction-associated steatotic liver disease (MASLD), a globally prevalent metabolic condition, is increasingly linked to impaired mitophagy. However, its regulatory mechanisms in MASLD are not fully elucidated. This study investigated the role of Zinc finger protein 143 (ZNF143) in regulating hepatocyte mitophagy during MASLD development and the mechanisms involved. We employed two complementary MASLD models: (1) C57BL/6J mice fed a high-fat diet (HFD) for 16 weeks and (2) Huh-7 cells exposed to free fatty acid (FFA). Pathological changes were detected by H&E Staining. Cellular lipid deposition and mitochondrial damage were assessed using Oil Red O, JC-1 staining and transmission electron microscope (TEM), respectively. The intermolecular interaction was identified by dual-luciferase reporter assay, ChIP, and Co-IP. ZNF143 was upregulated in MASLD models, and its knockdown mitigated lipid accumulation and liver injury by activating hepatocyte mitophagy. ZNF143 promoted SMAD-specific E3 ubiquitin-protein ligase 1 (SMURF1) transcription by binding to its promoter region. Moreover, SMURF1 mediated transient receptor potential vanilloid type 1 (TRPV1) ubiquitination and degradation. Finally, knockdown of TRPV1 or overexpression of SMURF1 reversed the promoting effect of ZNF143 knockdown on mitophagy in FFA-treated Huh-7 cells. In short, ZNF143 upregulation exacerbated MASLD progression by mediating TRPV1 ubiquitination and degradation through transcriptionally activating SMURF1.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent PIK3CA-E545K mutation promotes cervical cancer growth and invasion via AKT/mTOR signaling.","authors":"Congxiu Huang, Wei Zhang, Xiaoyu Ma, Xuefeng Li, Xiaoge Sun","doi":"10.1007/s00438-026-02495-z","DOIUrl":"10.1007/s00438-026-02495-z","url":null,"abstract":"<p><p>Cervical cancer remains a leading cause of cancer-related morbidity and mortality among women worldwide. Although genomic alterations in oncogenic signaling pathways have been implicated in cervical carcinogenesis, the functional impact of recurrent driver mutations remains incompletely understood. Whole-exome sequencing was performed on paired tumor and matched non-tumor tissues from 61 patients to identify recurrent somatic alterations. Functional significance was subsequently evaluated using cervical cancer cell models through proliferation, invasion, apoptosis, and signaling pathway analyses. Tumorigenic potential was further assessed using a xenograft mouse model. Genomic profiling identified PIK3CA as one of the most frequently mutated genes in cervical cancer. Functional analyses demonstrated that PIK3CA E545K mutation (PIK3CA-E545K-MUT) significantly enhanced tumor cell proliferation and invasive capacity while suppressing apoptosis. Mechanistically, these effects were associated with sustained activation of the AKT/mTOR signaling pathway, as evidenced by increased phosphorylation of key downstream effectors. Consistently, in vivo xenograft experiments confirmed that PIK3CA-E545K-MUT-driven signaling activation promoted tumor growth. Our findings establish a functional and mechanistic link between recurrent PIK3CA-E545K-MUT and aggressive tumor behavior in cervical cancer via AKT/mTOR pathway activation. These results provide experimental support for targeting the PI3K/AKT/mTOR axis as a potential therapeutic strategy in cervical cancer.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole exome sequencing uncovers novel genetic insights into Tethered cord syndrome.","authors":"Shuang Liu, Benzhang Tao, Gan Gao, Feng Zhang, Shuyan Tang, Lei Hou","doi":"10.1007/s00438-026-02490-4","DOIUrl":"10.1007/s00438-026-02490-4","url":null,"abstract":"<p><p>Tethered cord syndrome (TCS) is a neurodevelopmental disorder associated with neural tube defects (NTD), yet its genetic underpinnings remain poorly characterized. To elucidate its molecular basis, we conducted whole-exome sequencing (WES) on 81 TCS patients. Our analysis revealed that MNX1 variants, including two microdeletions and a deleterious missense variant, accounted for 3.7% (3/81) of cases in this cohort. Furthermore, gene-based collapsing analysis against 5,000 healthy controls revealed eight genes significantly enriched for loss of function variants and nine genes with an excess burden of damaging missense variants in TCS patients. Additionally, TCS patients exhibited a significantly higher burden of damaging missense variants in NTD-related genes. We also identified a trigenic variant combination (AFDN/PCSK5/PRICKLE4) exclusively in TCS patients, suggesting potential oligogenic inheritance in TCS. Collectively, our findings expand the genetic architecture of TCS, highlight novel pathogenic mechanisms, and provide insights for future clinical surveillance.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate derived from CAFs mediates H3K18la in stemness gene promoters, which promotes tumor malignant phenotype formation.","authors":"Jie Yao, Guangbin Li, Ke Chen, Yuxuan Wang, Xiaochen Lu, Jiaxi Li, Haitao Ma","doi":"10.1007/s00438-026-02460-w","DOIUrl":"10.1007/s00438-026-02460-w","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, characterized by high invasiveness, poor prognosis, and limited therapeutic options. Cancer-associated fibroblasts (CAFs), as a core component of the tumor microenvironment (TME), have been shown to promote the malignant progression of NSCLC, but the specific regulatory mechanisms remain incompletely understood. This study aims to investigate the role of CAFs and their metabolic products, particularly lactate, in the progression of NSCLC. CAFs and normal fibroblasts (NFs) were cultured, and the conditioned media (CM) were collected and used to treat NSCLC cells. Cell proliferation was assessed using CCK-8 and EdU assays, while cell migration was evaluated through transwell assays. The expression of E-cadherin and N-cadherin was detected by immunofluorescence (IF). Additionally, lactate levels, gene expression, and lactylation levels were assessed using a lactate detection kit, RT-qPCR, Western blot (WB), and chromatin immunoprecipitation (ChIP). The CM from CAFs enhanced the proliferation, migration, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Our experiments revealed that the metabolites from CAFs, particularly lactate, had a promoting effect on NSCLC. In lactate-treated NSCLC cells, the expression levels of stemness genes were significantly upregulated, accompanied by increased lactylation levels of H3K18. In in vivo experiments, tumors from the lactate treatment group exhibited higher growth rates and increased expression of stemness genes. Furthermore, human NSCLC tumor tissues showed significant upregulation of stemness genes. This study demonstrates that lactate derived from CAFs promotes the expression of stemness genes by mediating H3K18 lactylation in the promoters of these genes in NSCLC cells, thereby accelerating the malignant phenotype formation of NSCLC cells. These findings provide new insights into the role of CAFs in the TME and identify potential therapeutic targets for NSCLC.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-SSR architecture in Acrossocheilus fasciatus links cross-assembly repeat conservation, repeat-unit count variation, and genomic context.","authors":"Kai Liu, Nan Xie","doi":"10.1007/s00438-026-02489-x","DOIUrl":"10.1007/s00438-026-02489-x","url":null,"abstract":"<p><p>Microsatellites, or simple sequence repeats (SSRs), are abundant genomic features, but their evolutionary interpretation is often limited by detector-dependent discovery and single-reference surveys that count repeats without resolving homologous repeat states. We characterized pan-SSR architecture in the cyprinid Acrossocheilus fasciatus by integrating four genome assemblies within the AF_xajfe coordinate system. Synthetic ground-truth calibration identified Tandem Repeats Finder as the most accurate and parameter-stable algorithm, and coordinate-anchored merging resolved 499,190 pan-SSR entries comprising 39,150 core, 235,720 dispensable, and 224,320 private components. In homologous shared components, repeat-unit count variation dominated polymorphism (26.2% of core and 22.4% of dispensable SSRs), whereas motif mutations and mixed polymorphisms each remained near 1%. Genomic context differed among categories: core SSRs were preferentially associated with genes and promoters, private SSRs showed the highest classified transposable element overlap, and DNA transposons showed the strongest local association. At 1-Mb genomic resolution, SSR density was inversely associated with GC content (Pearson r = -0.485; Spearman ρ = -0.547), indicating scale-dependent constraints on repeat accumulation. Independent resequencing of 130 libraries from eight river populations showed that neutral/core and gene-associated/core sets could be genotyped in low-depth short-read data and retained population-informative repeat-unit dosage variation, including separation of the QingYiJiang group in weighted principal-component summaries. Together, these results provide a detector-calibrated, coordinate-anchored strategy for repeat evolutionary analysis in non-model vertebrates by comparing homologous SSRs across heterogeneous public assemblies and show that repeat-unit count variation, gene- and transposable-element-associated context, GC background, and short-read genotypability jointly organize the pan-SSR landscape.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-population proteome-wide mendelian randomization study identifies likely causal proteins for cardiovascular diseases.","authors":"Hua Zhong, Jingjing Zhu, Shuai Liu, Hoi Tung Hilton Wong, Yiqiang Zhang, Hung N Luu, Qing Wu, Xuexia Wang, Lang Wu","doi":"10.1007/s00438-026-02458-4","DOIUrl":"10.1007/s00438-026-02458-4","url":null,"abstract":"<p><p>Blood proteins may play causal roles in cardiovascular diseases (CVDs) such as heart failure (HF) and peripheral artery disease (PAD). Proteome-wide Mendelian randomization (MR) has been widely used to prioritize drug targets for CVD in European populations, but its application to non-European populations remains limited. We conducted a proteome-wide MR analysis to evaluate the potential causal effects of 2,922 plasma proteins on five CVDs-atrial fibrillation (AF), coronary artery disease (CAD), HF, ischemic heart disease (IHD), and PAD. Analyses were performed across African (n = 931), East Asian (n = 262), and European (n = 10,840) populations using genetic instrument data from the UK Biobank cohort. Significant associations were further examined with genetic colocalization to strengthen causal inference. Using MR and colocalization analyses, we identified 53 significant protein-CVD associations across multi-populations, including 16 in African, six in East Asian, and 31 in European populations, respectively. Cross-population comparisons revealed four protein-CVD associations unique to African population and another four specific to East Asian population. Integration with clinical trial data prioritized 14 protein-disease pairs as promising candidates for therapeutic development or drug repurposing. Our findings highlight the value of proteome-wide MR in evaluating drug target applicability across populations. Several protein-disease associations were population-specific, emphasizing the need for inclusive genetic research to inform precision medicine in CVD prevention and treatment.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}