Molecular Genetics and Genomics最新文献

{"title":"UCMSC-derived exosomal circDLGAP4 enhances HFF-1 cell proliferation and migration by promoting ZNF217 promoter H3K27 acetylation.","authors":"Yun-Lei Ma, Jia Fu, Yao-Xue Zhang, Han-Yue Xue, Yue-Yue Luo, Wei-Zhe Zhang, Shao-Jia Kuang, Jia-Qin Xu, Zun-Hong Liang","doi":"10.1007/s00438-026-02451-x","DOIUrl":"10.1007/s00438-026-02451-x","url":null,"abstract":"<p><p>Umbilical cord mesenchymal stem cells (UCMSCs) have been shown to actively participate in diabetic foot ulcer (DFU) wound healing. The human foreskin fibroblast-1 (HFF-1) cell line is a crucial and widely used in vitro model for fundamental research on DFUs. In this study, the role of UCMSC-derived exosomal circDLGAP4 in high-glucose (HG)-stressed HFF-1 cells was clarified, in particular whether it regulates the TATA-box binding protein-associated factor 15 (TAF15)/p300/zinc finger protein 217 (ZNF217) axis to enhance cell proliferation and migration. We confirmed that UCMSC-derived exosomes that contained circDLGAP4 in abundance enhanced the proliferation and migration of HG-stressed HFF-1 cells. Under an HG environment, ZNF217 was downregulated in the HFF-1 cells, whereas its overexpression promoted the proliferation and migration of the cells, an effect facilitated by its own activation via the p300-mediated H3K27 acetylation of its gene promoter. The p300 mRNA was stabilized through interaction with TAF15, while the expression of TAF15 was upregulated through its interaction with circDLGAP4. Additionally, exosomal circDLGAP4 promoted wound healing in mice with DFUs. In conclusion, UCMSC-derived exosomal circDLGAP4 enhanced HFF-1 cell proliferation and migration under HG conditions in vitro and promoted diabetic wound healing in vivo by activating the TAF15/p300/ZNF217 axis.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148032675","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":"Berberine impedes the DNA damage repair to inhibit colorectal cancer by regulating the SOX17/TCF4/PIM3 axis.","authors":"Fan Hu, Wei Wang, Mei Li, Qian Shi, Junjie Que, Pan Huang","doi":"10.1007/s00438-026-02439-7","DOIUrl":"10.1007/s00438-026-02439-7","url":null,"abstract":"<p><p>High levels of DNA damage repair (DDR) can promote the survival, immune evasion, and drug resistance of colorectal cancer (CRC) cells, consequently facilitating the advancement of CRC. This study was designed to investigate the inhibitory effect of berberine (BBR) on CRC progression and the underlying mechanism involving DDR regulation, to provide a novel theoretical basis for clinical CRC treatment. First, we found that BBR demonstrated a dose-dependent inhibition of the viability of CRC cells. BBR promoted apoptosis and suppressed the DDR in CRC cells by upregulating SOX17. Overexpression of SOX17 restrained CRC cell viability and facilitated cell apoptosis. BBR inhibited the DDR of CRC cells by inactivating the β-catenin/TCF4 pathway through the regulation of SOX17. Furthermore, TCF4 transcriptionally activated PIM3 expression. Knockdown of SOX17 partially eliminated the suppressive effects of BBR on CRC cell viability and DDR. Conversely, PIM3 silencing reversed the effects of SOX17 knockdown. In conclusion, we demonstrated BBR inhibits DDR in CRC cells via mediating the SOX17/TCF4/PIM3 axis, thereby blocking CRC progression. This regulatory axis serves as a potential therapeutic target for CRC, and BBR holds promising application prospects as a DDR inhibitor in CRC clinical intervention.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033103","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":"Genome-wide identification, in-silico characterization, and expression analysis of polygalacturonases in different fungal species.","authors":"Laiba Amin, Imran Zafar, Adil Jamal, Syed M Safeer Mehdi Bokhari, Fayez Saeed Bahwerth, Muhammad Noman","doi":"10.1007/s00438-026-02455-7","DOIUrl":"10.1007/s00438-026-02455-7","url":null,"abstract":"<p><p>Polygalacturonases (PGs) are key enzymes that hydrolyze pectin, a complex polysaccharide in plant cell walls, with essential roles in biological processes and industrial applications. This study presents a comprehensive genome-wide identification and in-silico characterization of PGs from four fungal species: Aspergillus oryzae, Aspergillus flavus, Neurospora crassa, and Rhizoctonia solani. A total of 44 PG protein sequences were retrieved from the NCBI database, confirming the presence of the Glyco_hydro_28 (GH28) domain, which is essential for pectin hydrolysis. Phylogenetic analysis using the Neighbor-Joining method revealed four major clades (A, B, C, D), with A. flavus and A. oryzae sharing a close evolutionary relationship (bootstrap support = 93%). Gene structure analysis revealed that A. flavus (Af1) and A. oryzae (Ao1) each have one exon, while Neurospora crassa (NSc1) contains one intron. Ten conserved motifs were identified, with Motif 1 present in Rz1, Rz2, and Rz5, and Motif 2 in all sequences except Ao15 and Ao16. Chromosomal mapping indicated species-specific gene distributions, with A. oryzae showing genes spread across five chromosomes. Gene expression analysis of A. oryzae under various growth conditions revealed 20 differentially expressed genes (DEGs), including 10 upregulated (e.g., Gene_Ao1, LFC = 2.50, FDR = 0.00450) and 10 downregulated (e.g., Gene_AO9, LFC = -2.87, FDR = 1.1e-05). Pathway enrichment analysis highlighted significant involvement of PGs in apoptosis (FDR = 1.2e0^-03), cell cycle regulation (FDR = 9.7e^-03), and DNA repair (FDR = 2.3e^-02). Protein-protein interaction (PPI) network analysis revealed 41 nodes and 400 edges, with an average node degree of 19.5. Structural modeling of the expressed protein LOCUS (XP_Ao1820953) with PDB ID: 5ZU2 showed high stability and flexibility, supported by molecular dynamics simulations. These results provide new insights into the evolutionary, structural, and functional roles of fungal PGs, with implications for their applications in biofuel production, food processing, and fiber retting.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033156","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":"Targeting KIF18B overcomes oxaliplatin resistance in esophageal squamous cell carcinoma via suppression of the ATR/CHK1 axis.","authors":"Wei Liu, Qianru Wang, Xiao Tan, Chunyu Cao, Bole Tian","doi":"10.1007/s00438-026-02440-0","DOIUrl":"10.1007/s00438-026-02440-0","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is aggressive with poor prognosis, frequently driven by chemotherapy resistance. Kinesin family member 18B (KIF18B) is implicated in tumor progression, but its role in ESCC chemoresistance remains unclear. To investigate KIF18B's clinical relevance and mechanistic contribution to oxaliplatin resistance in ESCC, KIF18B expression was analyzed in TCGA data, ESCC cell lines/tissues (qPCR, Western blot, IHC), and correlated with survival (Kaplan-Meier). Results showed that, KIF18B was significantly elevated in ESCC and correlated with shorter overall/progression-free survival. Knockdown reversed oxaliplatin resistance, reducing IC50 from 8.5 µM to 3 µM, restoring apoptosis, and inducing G2/M arrest. Silencing suppressed the ATR/CHK1 pathway (reduced p-ATR, p-CHK1, WEE1, CDC25A) and increased γH2AX foci. Co-IP confirmed KIF18B-ATR interaction, suggesting stabilization of DNA damage signaling. In vivo, KIF18B knockdown synergized with oxaliplatin, achieving > 80% tumor suppression and reduced Ki-67/p-ATR/p-CHK1 levels. In conclusion, KIF18B is a prognostic biomarker and therapeutic target in ESCC. Its inhibition overcomes oxaliplatin resistance by disrupting KIF18B-ATR interaction and ATR/CHK1-mediated DNA repair. Combining KIF18B targeting with chemotherapy or ATR inhibitors represents a promising strategy for refractory ESCC.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033127","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":"The causality between physical activity and gestational diabetes mellitus: a Mendelian randomization study.","authors":"Xiaoyan Ma, Yanqiu Liu, Xia Xu, Hua Wang, Xiaosu Zhao","doi":"10.1007/s00438-026-02430-2","DOIUrl":"10.1007/s00438-026-02430-2","url":null,"abstract":"<p><p>Although observational research shows that physical activity and sedentary behavior are associated with the risk of gestational diabetes mellitus (GDM), lipid, and body mass index (BMI), their causal direction and potential mediating mechanism are still unclear, which limits the development of precise prevention strategies. Based on the genetic data on the European ancestry population, the study aimed to investigate the causal relationship of GDM with physical activity and sedentary behavior using Mendelian randomization (MR), and quantify the mediating roles of BMI and lipids in it. The bidirectional dual sample MR analysis based on whole genome association research data revealed that there was a significant negative causal association between physical activity time and the risk of GDM in females (OR = 0.977, 95% CI: 0.956-0.998, P = 0.030), while leisure screen time had a positive causal association with the risk of developing GDM (OR = 1.125, 95% CI: 1.023-1.238, P = 0.015). Mediation analysis indicated that BMI was the primary causal pathway for reducing the risk of GDM through physical activity time, with a mediation ratio of 53.6%. Multivariate MR analysis showed that after adjusting for BMI, the direct effect was no longer significant, indicating that BMI played a major and almost complete mediating role. In the causal pathway of increased GDM risk in leisure screen time, BMI, high-density lipoprotein cholesterol (HDL-C), and Apolipoprotein A1 (ApoA1) effectively mediated the causal relationship between leisure screen time and GDM risk, with mediation proportions of 81.8%, 11.2% and 10.1%, respectively. Physical activity can indirectly reduce the risk of GDM by lowering BMI, while excessive leisure screen time significantly increases the risk of GDM by affecting BMI, HDL-C, and ApoA1. These findings support the potential value of prioritizing weight control and integrating interventions that increase physical activity and limit sedentary behavior as core measures, in order to fundamentally block the pathway of GDM by synergistically optimizing weight and lipid metabolism.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033172","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":"FAM72A is associated with lung cancer proliferation and migration via the NF‑κB signaling pathway.","authors":"Qinhua Gu, Qibin Shen, Tiancheng Liu, Lili Jin, Weiwei Min","doi":"10.1007/s00438-026-02450-y","DOIUrl":"10.1007/s00438-026-02450-y","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer-related deaths worldwide. While the Family with sequence similarity 72 member A (FAM72A) gene has been implicated in various cancers, its role in lung cancer is yet to be determined. This study aimed to investigate the role of FAM72A in lung cancer and the underlying mechanism. Bioinformatic analysis of The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD) dataset revealed that FAM72A was significantly upregulated in lung adenocarcinoma tissues, and high FAM72A expression was closely associated with poor patient prognosis. Western blot analysis revealed that FAM72A protein expression was significantly upregulated in multiple lung cancer cell lines (A549, H1299, and H460) compared to normal lung epithelial cells. Through a series of assays including flow cytometry, MTT, clone formation, wound healing, and Transwell experiments, we demonstrated that knockdown of FAM72A via shRNA effectively suppressed proliferation and migration in A549 and H1299 cells, while promoting apoptosis. Additionally, in vivo studies using a mouse xenograft model confirmed that FAM72A knockdown inhibited tumor growth. Mechanistic analyses showed that FAM72A knockdown is associated with inactivation of the NF‑κB signaling pathway, as knockdown led to decreased expression of p-IkBα, p-IKKα, p-NF-κB, Cyclin D1, and PCNA. In conclusion, our findings demonstrate that FAM72A contributes to lung cancer progression by regulating the activity of the NF‑κB signaling pathway, suggesting its potential as a therapeutic target for lung cancer.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006002","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":"Ecotype-specific sensitivity to DNA methylation inhibitors in Arabidopsis cmt3 mutants.","authors":"Xin Sun, Guo Du, Atsushi Kato, Hidetaka Ito","doi":"10.1007/s00438-026-02449-5","DOIUrl":"10.1007/s00438-026-02449-5","url":null,"abstract":"<p><p>DNA methylation inhibitors such as 5-aza-2'-deoxycytidine (5-Aza-2dC) are widely used to probe epigenetic regulation, yet genetic factors underlying natural variation in inhibitor sensitivity remain poorly understood. Here, we investigated ecotype-specific responses to 5-Aza-2dC in Arabidopsis thaliana, focusing on cmt3 mutants in the Columbia (Col-0) and Landsberg erecta (Ler) backgrounds. We found that cmt3 mutants displayed contrasting phenotypes depending on genetic background: Col-0 cmt3 mutants showed relative resistance to 5-Aza-2dC, whereas Ler cmt3 mutants exhibited pronounced sensitivity. Genetic analyses indicated that this enhanced sensitivity in the Ler background is recessive and cannot be explained solely by loss of CMT3 function. Through genetic mapping, we identified At1g34770 (NSE3) as a strong candidate modifier associated with 5-Aza-2dC sensitivity. A non-synonymous substitution in NSE3 correlated with growth inhibition under inhibitor treatment, and transgenic analyses further supported a contributory role for this gene. Together, our results demonstrate that natural genetic modifiers, including allelic variation in NSE3, shape ecotype-dependent responses to DNA methylation inhibition, highlighting the importance of genetic background in modulating epigenetic perturbations in plants.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974192","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":"Genome comparison of the bacteria in Mycobacterium avium complex (MAC) reveals the role of translational selection in shaping codon usage patterns.","authors":"Anindita Banerjee, Saubashya Sur","doi":"10.1007/s00438-026-02447-7","DOIUrl":"10.1007/s00438-026-02447-7","url":null,"abstract":"<p><p>The Mycobacterium avium complex (MAC) houses several pathogens that cause diseases in humans, ruminants, and birds. They are widely distributed in soils and water worldwide. In immunocompromised humans, MAC is responsible for nodular bronchiectasis and fibrocavitary lung diseases. The treatment of lung diseases induced by MAC remains difficult owing to antibiotic intolerance and disease recurrence. In this study, we compared the genome sequences of 90 complete MAC genomes and explored the factors shaping codon usage bias in the bacteria within MAC. Additionally, we studied the relationship between codon bias and pathogenic adaptation. The genome sizes ranged from 4.7 to 6.5 Mb. Variation in the mobile genetic elements and the number of CRISPR candidates was observed amongst the bacteria within MAC. Synonymous codon usage analysis divulged variations among subspecies, high codon usage bias, substantial heterogeneity in codon usage patterns, and moderate use of optimal codons. High GC3 content and elevated levels of CAI (a metric for gene expression levels) in all probability assisted the bacteria within MAC in adjusting to different host environments. Translational selection pressure prevailed over compositional bias and mutational selection in these organisms. Our analysis revealed differences in the tRNA content amongst the bacteria in MAC. The translational selective pressure enabled the adaptation of these pathogenic bacteria to competitive pressure in diverse environments and niches by maintaining a lesser number of tRNAs and lower tAI values.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973326","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":"Integrated transcriptomic and metabolomic investigation reveals that graphene oxide reduces nicosulfuron detriment in sweet corn.","authors":"Yanli Wang, Xuemei Zhong, Meng Zhang, Jian Wang","doi":"10.1007/s00438-026-02452-w","DOIUrl":"10.1007/s00438-026-02452-w","url":null,"abstract":"<p><p>Nicosulfuron (NIF) stress poses a significant constraint on sweet corn production. Graphene oxide (GO), as an environmentally friendly nanomaterial, serves as a safe agent to enhance crop stress resistance. However, the molecular mechanisms of GO-mediated sweet corn to tolerate NIF remain largely unexplored. This study aimed to investigate the regulatory effects of GO on sweet corn's response to NIF through physiological assessments, comparative transcriptomic analysis, and metabolomic profiling. The findings indicate that the application of GO mitigates the detrimental effects of NIF stress on sweet corn seedlings, as evidenced by enhanced growth metrics, improved chlorophyll fluorescence parameters, and photosynthetic indicators. GO predominantly influences genes and metabolites related to the synthesis of flavonoids, phenylpropanoids, and calcium (Ca²⁺) signaling pathways to counteract NIF stress in sweet corn. Additionally, key genes associated with peroxidases (POD) and cytochrome P450 monooxygenases (CYP) were identified through the analysis of weighted gene co-expression networks (WGCNA). These genes play crucial roles in the response to NIF stress orchestrated by graphene oxide. In summary, this study demonstrates the synergistic regulatory effect of GO on NIF tolerance in sweet corn, providing valuable insights for developing NIF-resistant sweet corn varieties.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973906","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":"ProSSF: integrating sequence, structure, and gene ontology for prediction of protein stability, interaction, and function.","authors":"Tongqiang Jiang, Yongshan Zhu, Zhenqiao Liu, Xiaowei Yi, Qingchuan Zhang, Shaoyi Song","doi":"10.1007/s00438-026-02433-z","DOIUrl":"10.1007/s00438-026-02433-z","url":null,"abstract":"<p><p>Protein sequences encode rich structural and functional information that governs how organisms respond to genetic variation, environmental challenge, and disease. However, existing computational methods typically rely on a single information source, whether sequence, structure, or functional annotation, and their predictive power is substantially reduced for low-homology proteins or orphan proteins. Here we present ProSSF (Protein Sequence-Structure-Function), a unified multimodal pretraining framework that performs masked pretraining on large-scale protein sequences, encodes three-dimensional structural information via a Geometric Vector Perceptron Graph Neural Network (GVP-GNN), integrates Gene Ontology (GO) semantics through a dual-path hierarchical encoder, and aligns all three modalities into a shared representation space via cross-modal attention. Evaluated across three downstream tasks, ProSSF achieves a Spearman correlation of 0.74 ± 0.009 on the TAPE protein stability benchmark, a mean Micro-F1 of 84.60% ± 0.9% on the SHS148K protein-protein interaction dataset under the stringent DFS partition, and comparable or superior Fmax and AUPR relative to state-of-the-art baselines across all three GO sub-ontologies. Ablation analyses demonstrate that structural geometry and GO functional semantics contribute complementary and task-dependent information, with the largest performance gains observed under low-homology conditions. Attention-based interpretability analyses further reveal that the model preferentially attends to biologically meaningful regions, such as kinase catalytic domains, without explicit supervision. This study provides a unified multimodal pretraining framework and demonstrates that jointly encoding sequence, structure, and functional semantics substantially improves the generalizability of protein property prediction. Future studies should validate this framework on larger, taxonomically diverse protein datasets and explore its potential applications in the functional annotation of disease-associated proteins and the identification of novel drug targets.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973961","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}