Gene最新文献

{"title":"Integration of transcriptome and targeted metabolome reveals regulatory and structural genes involved in anthocyanin biosynthesis of four Ceiba speciosa germplasms","authors":"Qingsong Bai ,&nbsp;Baozhu Zhu ,&nbsp;Yuxin Wang,&nbsp;Huanqin Liao,&nbsp;Xinyu Chen,&nbsp;Fang Xu,&nbsp;Weihua Zhang","doi":"10.1016/j.gene.2025.149762","DOIUrl":"10.1016/j.gene.2025.149762","url":null,"abstract":"<div><div><em>Ceiba speciosa</em> has become a common landscape tree species in southern China due to its abundant petal colors and ornamental application values. Until now, there is little knowledge relevant to the molecular mechanisms involved in petal color formation and phenotypical variations in this species. In this study, transcriptome and targeted metabolome were integrated for four types of germplasm resources with different petal colors to identify candidate regulators, structural genes, and anthocyanins that might be involved in the formation of petal colors. Through qualitative and quantitative analyses of anthocyanins, the contents of two cyanidins (Cyanidin-3,5-O-diglucoside and Cyanidin-3-O-glucoside) were both consistent with color trends among four types of cultivars. By using RNA-seq, several structural genes, including six PALs, three F3Hs, one CHI, one 4CL, two CHSs, two DFRs, one ANS, and seven GT1s, were identified to be involved in the pathway of anthocyanin biosynthesis and were differentially expressed and highly correlated with the content of at least one compound. Then, 12 core transcription factors, including seven MYBs (MYB-33, MYB-37, MYB-80, MYB-92, MYB-111, MYB-112, and MYB-121), two C3Hs (C3H-105 and C3H-106), one EIL (EIL-10), one GRAS (GRAS-53), and one G2-like (G2-like-1), were obtained and possibly related to petal color differentiation together with other co-expressed transcription factors. In addition, the expression of numerous members belongs to an MYB-bHLH-WD40 module, and the main transcription factors involved in regulating anthocyanin biosynthesis were also significantly correlated with the content of five important anthocyanins, which have the highest average contents among all the samples. Molecular co-expression networks were constructed to display the relationship among TFs, structural genes, and metabolites. Our study lays the foundation for revealing the molecular mechanism involved in flower color production and variations in <em>C. speciosa.</em></div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"969 ","pages":"Article 149762"},"PeriodicalIF":2.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046893","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":"Role of Notch and its oncogenic signaling crosstalk in glioma and glioma stem cells","authors":"Rajveer Singh Sidhu ,&nbsp;Shanchun Guo ,&nbsp;Guangdi Wang ,&nbsp;Mingli Liu","doi":"10.1016/j.gene.2025.149761","DOIUrl":"10.1016/j.gene.2025.149761","url":null,"abstract":"<div><div>Notch signaling (NS) is one of the primary regulators of Glioblastoma (GBM), which shapes tumour growth and evolution while protecting against drug treatments. Notch signaling enables Glioma stem cell (GSC) preservation in tumours, enhancing their diversity, and increasing tumour strength and resistance to treatment. Notch signaling keeps cancer cells growing and active through its ability to halt cell development while maintaining links with critical tumour pathways Wnt/β-catenin, PI3K/AKT, NF-kB, Hedgehog, and TGF-β. When signaling molecules communicate, they develop a strong system that enables tumour cells to survive longer and establish new blood vessels while resisting immune defenses and treatments. Developing treatments consisting of γ-secretase inhibitors, antibodies, and small molecule inhibitors show better outcomes when combined with other pathway-targeting approaches. Notch signaling may promote or inhibit cancer cell proliferation; it is crucial to detect unique biomarkers for each patient before developing individualized therapy regimens. The treatment of Notch-dependent tumours with PI3K/AKT or TGF-β inhibitors helps reduce resistance to therapy. The development of molecular techniques and single-cell analysis enables us to understand Notch signaling better for inventing treatment options specific to clinical settings. These approaches could be combined to improve the quality of life and speed up the recovery process for GBM patients. Notch signaling presents difficulties and possibilities that can guide new treatment options for GBM.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"969 ","pages":"Article 149761"},"PeriodicalIF":2.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039818","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":"Complex interplay of transcriptomic alterations, inflammatory cascades, and oxidative stress responses in a rat model of neonatal hypoxic-ischemic encephalopathy","authors":"Erzsebet Kovesdi","doi":"10.1016/j.gene.2025.149756","DOIUrl":"10.1016/j.gene.2025.149756","url":null,"abstract":"<div><div>In this edition of Gene’s “Editor’s Corner” we summarize the complex interactions of different molecular mechanisms behind the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). The topic is relevant, as the therapeutic options for HIE are limited, it is important to have as much knowledge as possible about the molecular processes underlying the disease. In the recent issue of Gene (Gene 952, 2025, 149363), Wang et al. used the neonatal rat model of HIE to shed light on the regulatory processes that have key roles in the brain’s response to this type of brain injury. They exposed rat pups to hypoxia with a modified Rice-Vannucci model to induce HIE. With different molecular biological tools and bioinformatic analyses they revealed the expression patterns of long non-coding RNAs, different inflammatory cytokines, micro RNAs, and oxidative stress markers which play important roles in the pathogenesis of HIE. They found 1000 differentially expressed long non-coding RNAs in the brain tissue, which is consistent with the fact that these are critical regulators of gene expression in various neurological disorders. They also found the upregulation of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and decrease of the anti-inflammatory cytokine IL-10. qRT-PCR revealed abnormal expression of several miRNAs. In addition, they found a significant decrease in the activity of superoxide dismutase and an increase in malondialdehyde in the rat brains. The presented findings by Wang et. al. are important, because they help us to better understand the pathogenesis behind HIE. Their new findings will hopefully enable the discovery of new diagnostic biomarkers and the therapeutic options, which will greatly contribute to the improvement of long-term neurological outcome of neonatal HIE.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"968 ","pages":"Article 149756"},"PeriodicalIF":2.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033100","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 SOX1:c.1036A > G:p.M346V variant act as an pathogenic gene in nasopharyngeal carcinoma","authors":"Guoqing Deng ,&nbsp;Peihu Li ,&nbsp;Changwu Li ,&nbsp;Caixia Li ,&nbsp;Yuanping Zhu ,&nbsp;Xianyao Jiang ,&nbsp;Kang Liao ,&nbsp;Yu Wu ,&nbsp;Qingchen Wei ,&nbsp;Jie Chen ,&nbsp;Kongning Li ,&nbsp;Bo Wang ,&nbsp;Hongyan Jiang","doi":"10.1016/j.gene.2025.149755","DOIUrl":"10.1016/j.gene.2025.149755","url":null,"abstract":"<div><h3>Background</h3><div>Nasopharyngeal carcinoma (NPC) pathogenesis is multi-factorial, involving synergistic interactions among genetic susceptibility, Epstein-Barr virus (EBV) infection, and environmental exposures. Notably, specific multi-generational families exhibit NPC incidence substantially exceeding both sporadic cases and general genetic susceptibility cohorts, demonstrating Mendelian inheritance patterns. This supports the hypothesis that high penetrance pathogenic variants dominate disease initiation and progression in familial NPC.</div></div><div><h3>Objective</h3><div>This study aims to identify such causal genes through systematic investigation of affected kindreds.</div></div><div><h3>Methods</h3><div>Through multi-generational pedigree analysis of a familial NPC, we identified putative pathogenic genes via integrated various data and the American College of Medical Genetics and Genomics (ACMG) variant interpretation. Subsequent targeted sequencing of NPC tissues enabled comprehensive profiling of candidate gene architecture, elucidating genotype-phenotype correlations in NPC oncogenesis.</div></div><div><h3>Results</h3><div>The <em>SOX1</em>:c.1036A &gt; G:p.M346V germline variant was classified as a “likely pathogenic” gene. A total of 161 <em>SOX1</em> mutation sites were detected in NPC tissues, <em>SOX1</em> variant sites escalates stepwise from sporadic NPC (5.67 ± 3.44) to family history NPC (12.28 ± 6.93, <em>p</em> &lt; 0.05 vs sporadic) and peaks in high variant allele frequency (VAF ≥ 20 %) lesions (17.16 ± 5.83, <em>p</em> &lt; 0.05 vs sporadic). <em>SOX1</em> high VAF mutations are enriched in family history NPC (27.8 %, 5/18) versus sporadic NPC (8.3 %, 1/12), and recurrent somatic mutations in <em>SOX1</em> demonstrate driver-like features.</div></div><div><h3>Conclusion</h3><div>The<!--> <em>SOX1</em>:c.1036A &gt; G:p.M346V variant represents a likely pathogenic driver in NPC, potentially exhibiting synergistic interactions with EBV-mediated oncogenesis. Concurrently, Somatic mutations at other <em>SOX1</em> sites demonstrate significant familial aggregation in NPC, implicating a tumor suppressor gene dosage-dependency model in tumorigenesis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"969 ","pages":"Article 149755"},"PeriodicalIF":2.4,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020495","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":"Identification of a carotenoid cleavage dioxygenase gene TeCCD4a regulating flower color and carotenoid content of marigold","authors":"Chunling Zhang ,&nbsp;Ke Zhu ,&nbsp;Chujun Huang ,&nbsp;Yuanzheng Yue ,&nbsp;Yanhong He","doi":"10.1016/j.gene.2025.149760","DOIUrl":"10.1016/j.gene.2025.149760","url":null,"abstract":"<div><div>Marigold (<em>Tagetes erecta</em>) serves as both an ornamental and economically significant species, owing to its diverse floral coloration and exceptionally high petal carotenoid content. Carotenoid cleavage dioxygenase (CCD), as the key enzymatic component, mediates the carotenoid degradation process. In this study, we cloned and functionally characterized a <em>CCD4</em> gene to elucidate its regulatory function in petal color and carotenoid biosynthesis. Our findings revealed that in the deep-orange marigold cultivar ‘Lady’, the expression of the <em>TeCCD4a</em> transcript initially increased before subsequently decreasing, reaching its peak at developmental stage S2. Conversely, in the cream-white cultivar ‘Vanilla’, <em>TeCCD4a</em> expression exhibited a steady rise throughout inflorescence development. Functional characterization revealed that overexpression of <em>TeCCD4a</em> in marigold induced a phenotypic transition of petal coloration from yellow to pale yellow, concomitant with metabolic alterations characterized by elevated accumulation of lycopene and violaxanthin, while reducing zeaxanthin and neoxanthin contents. In marigold transgenic lines, transcript levels of carotenogenic genes <em>TePDS</em>, <em>TeZDS</em>, and <em>TeHYDB</em> were upregulated, while <em>TeLCYB</em>, <em>TeZEP4</em>, and <em>TeCCD4b</em> were downregulated. Furthermore, promoter sequence analysis indicated that <em>TeCCD4a</em> expression may be regulated by multiple factors, as its promoter contains various <em>cis</em>-acting elements including light-responsive elements, stress-responsive elements, and hormone-responsive elements. This study provides a valuable gene resource and establishes a theoretical foundation for improving petal coloration and enhancing carotenoid accumulation in marigold.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"969 ","pages":"Article 149760"},"PeriodicalIF":2.4,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011186","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":"Identification of novel QTL associated with whitebacked planthopper (WBPH) and brown planthopper (BPH) resistance in the rice line RP2068","authors":"Nihar Sahu ,&nbsp;Sabhavat Bhaskar Naik ,&nbsp;G. Padmavathi ,&nbsp;Sunil S. Gangurde ,&nbsp;Manish K. Pandey ,&nbsp;Jagadish Sanmallappa Bentur ,&nbsp;Dhanasekar Divya","doi":"10.1016/j.gene.2025.149742","DOIUrl":"10.1016/j.gene.2025.149742","url":null,"abstract":"<div><div>This study aimed to identify QTL governing three traits of the resistance against the two planthoppers such as damage score (DS), nymphal survival (NS) and days to wilt (DW) using the 94 RIL population derived from the cross TN1/RP2068 utilizing 125 SSR and 1500 SNP markers. In case of the whitebacked planthopper (WBPH) five major and three minor QTL while for the brown planthopper (BPH) four major and seven minor QTL were identified to be associated with these three traits. Two major QTL, each on chromosomes 1 and 2, were responsible for DS and NS against WBPH accounted for 25% and 16% of the phenotypic variance (PVE). In addition, two QTL on chromosome 6 accounted for 17% (DS), 16% (NS) and one QTL on chromosome 8 accounted for 18% of the PVE for NS, respectively. As no QTL has been reported so far on chromosome 1 flanked by Fbox and RBO markers associated with WBPH resistance, we designed this locus as the novel QTL-<em>WBPH20(t)</em>. Against BPH, in addition, to the already reported <em>BPH33(t)</em> gene, two new QTL were identified on chromosomes 1 and 4 accounted for 21% &amp;, 17%, and 37% &amp;, 16% PVE for DS and NS, respectively. Significantly, a single locus on chromosome 1 flanked by RM1247 and SNP1715514 was found to be associated with both the planthoppers resistance. Based on <em>in silico</em> analysis and RNA sequencing data (published earlier), 21 putative candidate genes for WBPH and four for BPH were identified within these major QTL regions.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"969 ","pages":"Article 149742"},"PeriodicalIF":2.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011187","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 deficiency of DIP2C leads to congenital heart defects in patients with 10p15.3 microdeletion syndrome","authors":"Yu Xia ,&nbsp;Mingwen Zhang ,&nbsp;Rensheng Song ,&nbsp;Hongxiang Wu ,&nbsp;Jiangbo Deng ,&nbsp;Shufang Huang ,&nbsp;Yongchao Yang","doi":"10.1016/j.gene.2025.149753","DOIUrl":"10.1016/j.gene.2025.149753","url":null,"abstract":"<div><h3>Background</h3><div>Recurrent 10p15.3 microdeletion syndrome is a rare multisystem disorder characterized by abnormal facial features, global developmental delay (DD)/intellectual disability (ID), short stature, hand/foot malformation, and congenital heart defects (CHDs). However, the specific genetic defects that contribute to the cardiac phenotype remain unclear.</div></div><div><h3>Methods</h3><div>We explored the genetic cause of CHDs in 10p15.3 microdeletion syndrome. Antisense morpholino oligonucleotide (MO)-mediated knockdown of dip2ca in zebrafish and rescue experiments in zebrafish were conducted to observe the role of dip2ca in regulating cardiac growth. Expression profile analysis was conducted between the <em>dip2ca</em>-MO group and the control group.</div></div><div><h3>Results</h3><div>We report one male proband presenting a distinctive facial appearance, heterotropia, global DD/ID, congenital talipes equinovarus (CTEV), and atrial septal defect (ASD), who had a de novo 6.44 Mb microdeletion overlapping 10p15.3. We identified Disco Interacting Protein 2 Homolog C (DIP2C) as a putative candidate gene underlying CHDs by reviewing the 10p15.3 microdeletion cases with or without CHDs and performing candidate gene functional analysis. MO-mediated knockdown of <em>dip2ca</em> in zebrafish resulted in developmental defects consistent with the range of 10p15.3-associated human phenotypes include decreased body length, craniofacial malformations, and heart defects, including pericardial edema, a linear heart tube, looping defects, and arrhythmia. Coinjection of wild-type <em>dip2ca</em> mRNA with <em>dip2ca</em>-MO partially rescued these detects. Transcriptome analysis revealed the expression of zebrafish <em>foxj1a</em> increased in the <em>dip2ca</em>-MO zebrafish and was associated with cardiac looping.</div></div><div><h3>Conclusions</h3><div>This study expands the understanding of pathogenic genetic factors involved in 10p15.3 microdeletion syndrome and suggests that DIP2C plays an important role in heart development, especially with respect to cardiac looping.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"969 ","pages":"Article 149753"},"PeriodicalIF":2.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011185","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":"Capsaicin regulated lipid metabolism in HepG2 via mitochondrial autophagy PINK1/Parkin pathway","authors":"Hao Song ,&nbsp;Minhao Xie ,&nbsp;Hui Xu ,&nbsp;Jianhui Liu ,&nbsp;AnXiang Su ,&nbsp;YiZhou Liu ,&nbsp;Ye Wang ,&nbsp;Yongjiao Wang ,&nbsp;Fei Pei ,&nbsp;Wenjian Yang","doi":"10.1016/j.gene.2025.149752","DOIUrl":"10.1016/j.gene.2025.149752","url":null,"abstract":"<div><div>Capsaicin (CAP), a major natural functional component in chili peppers, has garnered considerable attention for its health benefits, including lipid-lowering effects, and its precise mechanisms remain unclear. This study aims to investigate the lipid-reducing effects of CAP on oleic acid (OA)-induced lipid accumulation in HepG2 cells and explore the underlying mechanisms. The results showed that CAP exerted lipid-lowering effects by reducing triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and increasing high-density lipoprotein cholesterol (HDL-C) in OA-induced HepG2 cells. CAP modulated the relative expression levels of lipid metabolism-related genes, including ACC, PPAR-α, PPAR-γ, Fasn, CPT-1, SREBP-1C, and SCD-1 in HepG2 cells. Notably, CAP activated the PINK1/Parkin-mediated mitophagy pathway to alleviatie lipid accumulation. Treatment with the mitophagy inhibitor Mdivi-1 reversed the lipid-lowering effect of CAP, and silencing PINK1 gene using siRNA abolished lipid-lowering effect of CAP in HepG2 cells, confirming the critical involvement of the pathway. In conclusion, CAP targeted the PINK1 gene and activated the PINK1/Parkin signaling pathway to promote mitophagy, restoring cellular energy homeostasis and regulating lipid synthesis and degradation, ultimately reducing lipid accumulation. These findings provided a mechanistic basis for the potential use of CAP in developing novel natural therapies for lipid metabolic disorders and obesity management.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"968 ","pages":"Article 149752"},"PeriodicalIF":2.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988840","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":"Progress and challenges in the use of Cofilin-1 as a prognostic and predictive biomarker for cancer management","authors":"Mariane Araujo Branco ,&nbsp;Bárbara Marquezin Kunst ,&nbsp;Brasil Silva Neto ,&nbsp;Fabio Klamt","doi":"10.1016/j.gene.2025.149746","DOIUrl":"10.1016/j.gene.2025.149746","url":null,"abstract":"<div><div>Cofilin-1 (<em>CFL1</em>) is an actin-regulating protein encoded by the <em>CFL1</em> gene and plays a central role in cytoskeletal dynamics, cell motility, and invasion—processes critical for tumor progression and metastasis. Aberrant <em>CFL1</em> expression has been linked to poor prognosis, therapeutic resistance, and increased metastatic potential across several human cancers. This review consolidates clinical evidence from studies involving human samples over the past 15 years, highlighting <em>CFL1</em> as a candidate prognostic and predictive biomarker. We analyze tumor-specific expression patterns, detection methodologies as immunohistochemistry, ELISA, proteomics and discuss regulatory pathways involving <em>CFL1.</em> Particular attention is given to prostate cancer, where the lack of reliable molecular biomarkers for risk stratification represents a clinical gap. Despite promising associations, the clinical translation of <em>CFL1</em> is hindered by heterogeneity in quantification protocols and limited prospective validation. We outline the key challenges and propose future directions to establish <em>CFL1</em> as a clinically actionable biomarker, with potential relevance to personalized cancer management.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"968 ","pages":"Article 149746"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988838","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":"A fragment in the 5′ untranslated region of alcohol oxidase 1 promoter significantly influencing gene expression of Komagataella phaffii","authors":"Aibo Feng,&nbsp;Ziwei Zhou,&nbsp;Wenjie Cong,&nbsp;Hualan Zhou,&nbsp;Jianguo Zhang","doi":"10.1016/j.gene.2025.149745","DOIUrl":"10.1016/j.gene.2025.149745","url":null,"abstract":"<div><div><em>Komagataella phaffii</em> is a famous microbial host in synthetic biology field for expressing heterologous proteins under alcohol oxidase 1 promoter (<em>P_AOX1</em>). This study undertook two successive rounds of gene fragment knockout, identifying a 13 bp segment, termed D3, as a negative <em>cis</em>-acting element in the 5′ untranslated region of <em>P_AOX1</em>. Notably, upon knockout of the D3 fragment, the expression of green fluorescent protein (GFP), serving as the model for heterologous protein expression, improved by 3.5-fold due to enhanced transcription levels. Subsequent transcriptomic analysis, electrophoretic mobility shift assay and DNA pull-down assays coupled with liquid chromatography-mass spectrometry corroborated efficient GFP expression, highlighting minimal alterations in transcriptional machinery subunits, 312 differentially expressed genes and non-specific interactions between nucleoproteins and <em>P_AOX1</em> following the D3 fragment knockout. Consequently, D3 fragment knock out from <em>P_AOX1</em> facilitates efficient expression of heterologous protein by <em>K. phaffii</em>.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"969 ","pages":"Article 149745"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992136","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}