Genes to Cells最新文献_第7页

Attenuation of Oxygen-Induced Neovascularization and Inflammation by Neutralizing VEGFA and/or ANG-2 With an Antibody 用抗体中和VEGFA和/或ANG-2抑制氧诱导的新生血管和炎症。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2026-04-07 DOI: 10.1111/gtc.70107

Hirokazu Oohashi, Toshiro Iwagawa, Hiroto Abe, Chihiro Kawaji, Yuta Inokuchi, Tetsuhiro Soeda, Kosuke Saita, Makoto Aihara, Sumiko Watanabe

{"title":"Attenuation of Oxygen-Induced Neovascularization and Inflammation by Neutralizing VEGFA and/or ANG-2 With an Antibody","authors":"Hirokazu Oohashi, Toshiro Iwagawa, Hiroto Abe, Chihiro Kawaji, Yuta Inokuchi, Tetsuhiro Soeda, Kosuke Saita, Makoto Aihara, Sumiko Watanabe","doi":"10.1111/gtc.70107","DOIUrl":"10.1111/gtc.70107","url":null,"abstract":"Neovascularization is a major cause of blindness in various retinal diseases, and inflammation aggravates the pathological and clinical conditions of these diseases. VEGFA or ANG-2 neutralizing antibodies have been used to block pathological neovascularization. In this work, the effects of intraocular administration of neutralizing antibodies against VEGFA, ANG-2, or bispecific to these two factors on pathological findings were examined in the oxygen-induced retinopathy (OIR) mouse model. At both postnatal day (P)17 and P19, anti-VEGFA and -ANG-2 administration suppressed neovascularization, and the bispecific antibody attenuated neovascularization more efficiently. However, oxygen-induced vaso-obliteration was not modified by these antibodies. Numbers of photoreceptor, amacrine, and bipolar cells were reduced in the OIR retina, and the antibodies reversed these changes. Microglia-specific gene expression increased in the OIR retina, and administration of the antibodies reduced the IBA1-positive area in the OIR retina, although these antibodies did not affect Iba1 gene expression. Labeled VEGFA and ANG-2 were found to be co-localized with microglia, suggesting that VEGFA and ANG-2 affect microglia activation directly. Taken together, neutralizing antibody to VEGFA or ANG-2 attenuated oxygen-induced neovascularization and inflammation, and the bispecific antibody more efficiently suppressed some features than the single antibody to VEGFA or ANG-2.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"31 3","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13055877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of the Growth-Inhibitory Activity of Fhl1 via Interaction With Ifh1 and Crf1 at the Ribosomal Protein Gene Promoters in Saccharomyces cerevisiae 酿酒酵母核糖体蛋白基因启动子上与Ifh1和Crf1相互作用调控Fhl1的生长抑制活性

IF 1.3 4区生物学

Genes to Cells Pub Date : 2026-04-07 DOI: 10.1111/gtc.70109

Naoki Shimamura, Koji Kasahara

{"title":"Regulation of the Growth-Inhibitory Activity of Fhl1 via Interaction With Ifh1 and Crf1 at the Ribosomal Protein Gene Promoters in Saccharomyces cerevisiae","authors":"Naoki Shimamura, Koji Kasahara","doi":"10.1111/gtc.70109","DOIUrl":"10.1111/gtc.70109","url":null,"abstract":"The transcription factor Fhl1, which binds to the promoters of the ribosomal protein genes (RPGs) in Saccharomyces cerevisiae, promotes transcription by recruiting the transcription activator Ifh1 under nutrient-rich conditions. During starvation, Ifh1 dissociates from the RPG promoter, and the transcriptional repressor Crf1 binds to Fhl1 instead of Ifh1, thereby suppressing transcription. However, the lethality of the ifh1Δ strain was suppressed by deletion of FHL1, suggesting that Ifh1 has essential functions beyond transcriptional activation. Detailed analyses using various deletion mutants of Fhl1 and Ifh1 revealed that the lethality of the ifh1Δ strain is suppressed by mutation of the forkhead-associated (FHA) domain, which interacts with the forkhead-binding (FHB) domains of Ifh1 and Crf1. Inducing Fhl1-expression in ifh1Δfhl1Δ strain suppressed growth, indicating that promoter-bound Fhl1 inhibits RPG transcription via an unknown mechanism. The lethality of ifh1Δ strain was suppressed by expression of the Ifh1 FHB domain from its native promoter or by overexpression of the corresponding domain of Crf1. These findings suggest that, while Fhl1 promotes transcription by recruiting Ifh1, dissociation of Ifh1 exposes the FHA domain, which triggers growth inhibition via an unknown mechanism. Binding to the FHA domain and neutralizing its inhibitory activity may represent a key function of Ifh1.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"31 3","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13054639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional Role of COP1 Gene in Hepatocellular Carcinoma Lipid Metabolism and Stemness COP1基因在肝癌脂质代谢和干细胞中的功能作用。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2026-04-06 DOI: 10.1111/gtc.70108

Eun-Hye Jeon, An-Na Bae, Hajin Lee, Keon Uk Park, Hyun Mu Shin, Jong Ho Park, Kwang Seok Kim, In-Chul Park, Yun-Han Lee

{"title":"Functional Role of COP1 Gene in Hepatocellular Carcinoma Lipid Metabolism and Stemness","authors":"Eun-Hye Jeon, An-Na Bae, Hajin Lee, Keon Uk Park, Hyun Mu Shin, Jong Ho Park, Kwang Seok Kim, In-Chul Park, Yun-Han Lee","doi":"10.1111/gtc.70108","DOIUrl":"10.1111/gtc.70108","url":null,"abstract":"We have previously defined the constitutive photomorphogenic protein 1 (COP1) gene as a therapeutic target in hepatocellular carcinoma (HCC). A recent study demonstrated that COP1 induces non-alcoholic fatty liver disease (NAFLD), a precursor to HCC, in normal hepatocytes and that reducing COP1 expression significantly improves high-fat diet-induced hepatic steatosis. Thus, in this study, we investigated if the function of COP1 was associated with HCC metabolism and evolution. Silencing of COP1 expression by a target siRNA significantly suppressed long-term colony formation in Huh7, HepG2, Huh1, and PLC/PRF/5 HCC cell lines. RNA sequencing of COP1-silenced Huh7 and HepG2 cells revealed the same directional regulation of 24 (14 up- and 10 down-regulated) genes. Notable molecular alterations were upregulation of AKR1D1 and downregulation of TMEM65, which involves negative regulation of lipid metabolism and promotion of metastasis, respectively. Correlation analysis using GEPIA2 supported inverse relationship between COP1 and AKR1D1 expression and positive relationship between COP1 and TMEM65 expression in HCC clinical samples. Targeting of COP1 reduced fat accumulation and metastatic potential in both HCC parental cells and CD133+ liver cancer stem cells. Overexpression of COP1 reversed the phenotypic changes. Collectively, our findings indicate that the COP1 is functionally correlated with HCC lipid metabolism and stemness.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"31 3","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147625388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Mechanism of Caspase-8–Dependent Interleukin-18 Activation in Pancreatic Cancer Cells Induced by 5-Fluorouracil and Nutrient Starvation 5-氟尿嘧啶和营养饥饿诱导胰腺癌细胞中caspase -8依赖性白介素-18活化的分子机制

IF 1.3 4区生物学

Genes to Cells Pub Date : 2026-04-06 DOI: 10.1111/gtc.70111

Hiroki Kamino, Yuko Nariai, Takeshi Urano

{"title":"Molecular Mechanism of Caspase-8–Dependent Interleukin-18 Activation in Pancreatic Cancer Cells Induced by 5-Fluorouracil and Nutrient Starvation","authors":"Hiroki Kamino, Yuko Nariai, Takeshi Urano","doi":"10.1111/gtc.70111","DOIUrl":"10.1111/gtc.70111","url":null,"abstract":"Interleukin-18 (IL-18) is a pro-inflammatory cytokine, and higher IL-18 expression in pancreatic tumors is associated with poor prognosis. Although 5-fluorouracil (5-FU) has been reported to induce the release of bioactive (mature/cleaved) IL-18 from the pancreatic cancer cell line Capan-2, the underlying mechanism remains unclear. Here, we investigated IL-18 activation in pancreatic cancer cells after 5-FU treatment under low-nutrient conditions that mimic key features of the tumor microenvironment, using a monoclonal antibody we generated that specifically recognizes cleaved, active IL-18. We detected the release of active IL-18 from both Capan-2 and MIA PaCa-2 cells after 5-FU treatment. Analysis of separated attached and detached cell fractions showed that IL-18 cleavage occurred predominantly in detached cells. We also clarified that caspase-8—but not caspase-1/4—was activated in detached cells and was required for IL-18 and GSDMD cleavage that is a hallmark of pyroptosis. Surprisingly, detached cells from only nutrient starvation showed the same phenomenon, and 5-FU contributed to increased pyroptotic cells. On the other hand, the release of active IL-18 was not observed with gemcitabine. These findings suggest that a low-nutrient tumor microenvironment and 5-FU therapy can promote caspase-8–dependent pyroptotic cell death with IL-18 activation, potentially contributing to chronic inflammation in pancreatic tumors.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"31 3","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147625359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The I-BAR Protein baiap2l1a Is Required for Protrusion and Lateral Elongation of Microridges I-BAR蛋白baiap2l1a是微脊突出和侧伸所必需的。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2026-04-06 DOI: 10.1111/gtc.70101

Yasuko Inaba, Kimika Iwasaki, Aoi Nakamura, Shiro Suetsugu, Yasumasa Bessho

{"title":"The I-BAR Protein baiap2l1a Is Required for Protrusion and Lateral Elongation of Microridges","authors":"Yasuko Inaba, Kimika Iwasaki, Aoi Nakamura, Shiro Suetsugu, Yasumasa Bessho","doi":"10.1111/gtc.70101","DOIUrl":"10.1111/gtc.70101","url":null,"abstract":"<div>\u0000 \u0000 Microridges are laterally elongated membrane protrusions of epithelial cells. Microridges are arranged in maze-like patterns and found on various mucosal epithelia, including the skin of zebrafish, where they are required to maintain mucus. The molecular mechanism that deforms epithelial membranes to create microridges remains unknown. We have found that one of the I-BAR domain proteins, baiap2l1a, which regulate membrane curvature, is required for microridge morphogenesis. Baiap2l1a mutant zebrafish had shorter and wider microridges. Baiap2l1a localized to microridges, and preceded microridge formation. Structure/function experiments revealed that the I-BAR domain could partially rescue microridge length in mutants. A 39 amino acid deletion in the I-BAR domain caused the loss of one α-helix, is sufficient to impair microridge localization and microridge elongation. These results suggest that the intact I-BAR domain structure is required for baiap2l1a microridge localization and function. Eps8like1a genetically interacted with baiap2l1a in microridge elongation. We found that the membrane curvature protein baiap2l1a plays an important role in microridge formation.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"31 3","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147625419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient Induction of Oligodendrocyte Lineage From Pluripotent Stem Cells via Temporal Modulation of OLIG2(S147A) and SOX10 通过调控OLIG2（S147A）和SOX10从多能干细胞高效诱导少突胶质细胞谱系。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2026-04-02 DOI: 10.1111/gtc.70106

Mitsuru Ishikawa, Yoshiki Izumizawa, Sopak Supakul, Hideyuki Okano

{"title":"Efficient Induction of Oligodendrocyte Lineage From Pluripotent Stem Cells via Temporal Modulation of OLIG2(S147A) and SOX10","authors":"Mitsuru Ishikawa, Yoshiki Izumizawa, Sopak Supakul, Hideyuki Okano","doi":"10.1111/gtc.70106","DOIUrl":"10.1111/gtc.70106","url":null,"abstract":"<div>\u0000 \u0000 Several protocols for generating oligodendrocytes (OLs) from human pluripotent stem cells have been reported. However, they are limited by long culture duration, intensive handling, and low yield of mature OLs. Transcription factor-based strategies have improved efficiency, but OLIG2 and SOX10, key regulators of oligodendrocyte precursor cells (OPCs), also promote alternative neural fates. Here, we developed a Tet-inducible system to control SOX10 and OLIG2 expression, including that of a phosphorylation-deficient OLIG2 mutant (S147A). Co-expression of SOX10 and OLIG2 enhanced OPC induction, confirmed by O4 positivity and transcriptomic profiling. Interestingly, only a brief induction of SOX10 + OLIG2(S147A) (2–5 days) efficiently yielded myelin basic protein positive OLs within 25 days, reaching approximately 20% of total cells. In contrast, sustained doxycycline-mediated expression of SOX10 and OLIG2(S147A) favored OPC proliferation and delayed OL maturation. These findings highlight the importance of temporal control of transcription factor activity in accelerating OL differentiation and provide a practical platform for disease modeling and regenerative applications.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"31 3","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

International Symposium on Protein and Organelle Lifetime Regulation (ISPO2025): From Turnover Mechanisms to Targeted Control 蛋白质和细胞器寿命调节国际研讨会（ISPO2025）：从周转机制到目标控制。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2026-03-29 DOI: 10.1111/gtc.70104

Shigeo Murata, Jun Hamazaki, Yuri Shibata

{"title":"International Symposium on Protein and Organelle Lifetime Regulation (ISPO2025): From Turnover Mechanisms to Targeted Control","authors":"Shigeo Murata, Jun Hamazaki, Yuri Shibata","doi":"10.1111/gtc.70104","DOIUrl":"10.1111/gtc.70104","url":null,"abstract":"<div>\u0000 \u0000 The International Symposium on Protein and Organelle Lifetime Regulation (ISPO2025) was held on 30 October–2 November 2025 at Nara Kasugano Forum Iraka, Nara, Japan. The meeting was organized by the core members of the Transformative Research Areas (A) project “Shin-Biology Regulated by Protein Lifetime,” and brought together 195 participants (150 from Japan and 45 from abroad). The program comprised 11 oral sessions, 16 invited lectures by speakers from overseas, and 83 posters. Topics spanned proteasome-mediated and autophagy-mediated pathways underlying protein and organelle turnover, quantitative technologies to measure these processes with accuracy and depth, and chemical approaches to modulate protein and organelle degradation. The Keiji Tanaka Memorial Session opened the symposium, honoring his legacy in proteasome biology and intracellular proteolysis. Across the meeting, protein and organelle lifetime emerged as measurable and comparable readouts connecting molecular mechanisms to disease-relevant cellular states and therapeutic strategy, while also unifying proteome remodeling, organelle quality control, and drug discovery.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"31 3","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct Behavioral Roles of D-Aspartate Oxidases DDO-1 and DDO-2 in Caenorhabditis elegans d -天冬氨酸氧化酶DDO-1和DDO-2在秀丽隐杆线虫中的不同行为作用

IF 1.3 4区生物学

Genes to Cells Pub Date : 2026-03-20 DOI: 10.1111/gtc.70103

Yasuaki Saitoh, Masumi Katane, Tetsuya Miyamoto, Masae Sekine, Hiroshi Homma

{"title":"Distinct Behavioral Roles of D-Aspartate Oxidases DDO-1 and DDO-2 in Caenorhabditis elegans","authors":"Yasuaki Saitoh, Masumi Katane, Tetsuya Miyamoto, Masae Sekine, Hiroshi Homma","doi":"10.1111/gtc.70103","DOIUrl":"10.1111/gtc.70103","url":null,"abstract":"<div>\u0000 \u0000 D-amino acids are widely distributed across organisms, and their metabolism contributes to the regulation of neuronal activity and behavior. Whereas most animals possess one D-amino acid oxidase (DAAO) for neutral and basic D-amino acids and one D-aspartate oxidase (DDO) for acidic D-amino acids, the nematode Caenorhabditis elegans uniquely carries three DDOs. Previous studies showed that DDO-3 affects the nose touch response and that DAAO-1 regulates foraging behavior after food removal. However, the physiological roles of DDO-1 and DDO-2 had remained unclear. Here, we analyzed loss-of-function mutants to examine the behavioral roles of D-amino acid–oxidizing enzymes in C. elegans. The ddo-1 mutant displayed reduced responses to posterior body touch and a disrupted defecation rhythm, whereas the ddo-2 mutant exhibited increased forward movement duration and reduced reversal frequency during foraging immediately after food removal. In wild-type animals, dietary D-Asp supplementation reduced the posterior body touch response, and oxaloacetate restored the defecation defects of ddo-1 mutants. In addition, acidic amino acid supplementation altered foraging-related locomotor behavior in wild-type animals but not in ddo-2 mutants. All behavioral defects were rescued in the corresponding transgenic lines. Together, these results indicate distinct behavioral roles of D-amino acid–oxidizing enzymes in C. elegans.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"31 2","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147492473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Introns as Protective Buffers Against Transposable Elements Invasion During Genome Gigantism in a Newt 在蝾螈基因组巨化过程中，内含子对转座因子入侵的保护缓冲。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2026-03-20 DOI: 10.1111/gtc.70102

Kazuto Bou, Kiyokazu Agata

{"title":"Introns as Protective Buffers Against Transposable Elements Invasion During Genome Gigantism in a Newt","authors":"Kazuto Bou, Kiyokazu Agata","doi":"10.1111/gtc.70102","DOIUrl":"10.1111/gtc.70102","url":null,"abstract":"Genome gigantism has long been linked to recurrent bursts of transposable element (TE) activity, yet how such bursts reshape gene architecture over evolutionary time remains poorly understood. By comparing two independently assembled genomes of the Iberian ribbed newt Pleurodeles waltl (20.3 Gb)—generated in Europe and Japan—with the compact genome of Xenopus tropicalis (1.5 Gb), we uncover evidence for both past and ongoing TE bursts during newt genome expansion. Analyses of multicopy genes reveal a spectrum of evolutionary outcomes driven by successive waves of intronic TE invasion. While some genes remain functional despite massive gene body inflation through efficient splicing-mediated removal of TE insertions, others undergo transcriptional silencing, followed by mutation accumulation, pseudogenization, and progressive disorganization of exon–intron architecture. Direct comparison between the two P Pleurodeles waltl assemblies demonstrates that TE insertions continue to occur, indicating that genome expansion is an active, ongoing process. We further identify Bou1, a testis-specific, TE-derived locus whose expression coincides with germline-associated TE activity. Together, these results depict genome gigantism as a punctuated yet persistent process and suggest that introns act as protective buffers against TE invasion, delaying gene decay until selective constraints are relaxed.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"31 2","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147489188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

5-Aza-Cytidine Enhances Terminal Polyadenylation Site Usage for Full-Length Transcripts in Cells 5-Aza-Cytidine增强细胞全长转录本末端聚腺苷化位点的使用

IF 1.3 4区生物学

Genes to Cells Pub Date : 2026-03-10 DOI: 10.1111/gtc.70100

Samuel Ogunsola, Ling Liu, Urmi Das, Jiuyong Xie

{"title":"5-Aza-Cytidine Enhances Terminal Polyadenylation Site Usage for Full-Length Transcripts in Cells","authors":"Samuel Ogunsola, Ling Liu, Urmi Das, Jiuyong Xie","doi":"10.1111/gtc.70100","DOIUrl":"10.1111/gtc.70100","url":null,"abstract":"<div>\u0000 \u0000 As an inhibitor of DNA methyltransferases (DNMTs) and an anti-cancer drug, 5-aza-cytidine (5-azaC)'s many effects on gene expression remain unclear. Here, we show that 5-azaC treatment of cultured GH3 pituitary tumor cells increases relative usage of genomic terminal exons (GTEs) across the transcriptome. This effect is largely achieved by shifting mRNA polyadenylation from proximal poly(A) sites to GTEs, which harbor a more optimal consensus motif of poly(A) signals. Consistent with this shift, 5-azaC upregulates the mRNA anti-termination factors Scaf4 and Scaf8 while downregulating the early termination enhancer E2f2. In MOLM-13 leukemia cells, 5-azaC similarly promotes the production of full-length transcripts and regulates alternative polyadenylation factors, some of which are in the same direction as observed in GH3 cells. Moreover, PCF11, a factor known to promote proximal poly(A) site usage, is upregulated in both cell lines, suggesting a homeostatic response by these cells to counteract transcript lengthening during 5-azaC treatment. Together, these findings uncover a previously unknown effect of 5-azaC on gene expression: directional promotion of terminal polyadenylation site usage, driving a transcriptome-wide switch from shortened to full-length mRNAs in tumor or cancer cells and consequently altering the alternative usage of multiple 3′ exons.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"31 2","pages":""},"PeriodicalIF":1.3,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147392231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0