Alexander T Lessenger, Jan M Skotheim, Mathew P Swaffer, Jessica L Feldman
{"title":"Somatic polyploidy supports biosynthesis and tissue function by increasing transcriptional output.","authors":"Alexander T Lessenger, Jan M Skotheim, Mathew P Swaffer, Jessica L Feldman","doi":"10.1083/jcb.202403154","DOIUrl":"10.1083/jcb.202403154","url":null,"abstract":"<p><p>Cell size and biosynthetic capacity generally increase with increased DNA content. Somatic polyploidy has therefore been proposed to be an adaptive strategy to increase cell size in specialized tissues with high biosynthetic demands. However, if and how DNA concentration limits cellular biosynthesis in vivo is not well understood. Here, we show that polyploidy in the Caenorhabditis elegans intestine is critical for cell growth and yolk biosynthesis, a central role of this organ. Artificially lowering the DNA/cytoplasm ratio by reducing polyploidization in the intestine gave rise to smaller cells with dilute mRNA. Highly expressed transcripts were more sensitive to this mRNA dilution, whereas lowly expressed genes were partially compensated-in part by loading more RNA Polymerase II on the remaining genomes. Polyploidy-deficient animals produced fewer and slower-growing offspring, consistent with reduced synthesis of highly expressed yolk proteins. DNA-dilute cells had normal total protein concentration, which we propose is achieved by increasing the expression of translational machinery at the expense of specialized, cell-type-specific proteins.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Selective regulation of kinesin-5 function by β-tubulin carboxy-terminal tails.","authors":"Ezekiel C Thomas, Jeffrey K Moore","doi":"10.1083/jcb.202405115","DOIUrl":"https://doi.org/10.1083/jcb.202405115","url":null,"abstract":"<p><p>The tubulin code hypothesis predicts that tubulin tails create programs for selective regulation of microtubule-binding proteins, including kinesin motors. However, the molecular mechanisms that determine selective regulation and their relevance in cells are poorly understood. We report selective regulation of budding yeast kinesin-5 motors by the β-tubulin tail. Cin8, but not Kip1, requires the β-tubulin tail for recruitment to the mitotic spindle, creating a balance of both motors in the spindle and efficient mitotic progression. We identify a negatively charged patch in the β-tubulin tail that mediates interaction with Cin8. Using in vitro reconstitution with genetically modified yeast tubulin, we demonstrate that the charged patch of β-tubulin tail increases Cin8 plus-end-directed velocity and processivity. Finally, we determine that the positively charged amino-terminal extension of Cin8 coordinates interactions with the β-tubulin tail. Our work identifies a molecular mechanism underlying selective regulation of closely related kinesin motors by tubulin tails and how this regulation promotes proper function of the mitotic spindle.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ariel L Gold, Matthew E Hurlock, Alicia M Guevara, Lilah Y Z Isenberg, Yumi Kim
{"title":"Identification of the Polo-like kinase substrate required for homologous synapsis.","authors":"Ariel L Gold, Matthew E Hurlock, Alicia M Guevara, Lilah Y Z Isenberg, Yumi Kim","doi":"10.1083/jcb.202408092","DOIUrl":"https://doi.org/10.1083/jcb.202408092","url":null,"abstract":"<p><p>The synaptonemal complex (SC) is a zipper-like protein structure that aligns homologous chromosome pairs and regulates recombination during meiosis. Despite its conserved appearance and function, how synapsis occurs between chromosome axes remains elusive. Here, we demonstrate that Polo-like kinases (PLKs) phosphorylate a single conserved residue in the disordered C-terminal tails of two paralogous SC subunits, SYP-5 and SYP-6, to establish an electrostatic interface between the SC central region and chromosome axes in C. elegans. While SYP-5/6 phosphorylation is dispensable for the ability of SC proteins to self-assemble, local phosphorylation by PLKs at the pairing center is crucial for SC elongation between homologous chromosome axes. Additionally, SYP-5/6 phosphorylation is essential for asymmetric SC disassembly and proper PLK-2 localization after crossover designation, which drives chromosome remodeling required for homolog separation during meiosis I. This work identifies a key regulatory mechanism by which localized PLK activity mediates the SC-axis interaction through phosphorylation of SYP-5/6, coupling synapsis initiation to homolog pairing.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenePub Date : 2025-02-10Epub Date: 2024-11-29DOI: 10.1016/j.gene.2024.149134
Yuchen Wu, Dongdong Wang, Jie Zhao, Jinhui Guo, Zhenyu Gao, Qiuran Xu, Xiaoge Hu
{"title":"NRAV promoted the malignant progression of gastric cancer.","authors":"Yuchen Wu, Dongdong Wang, Jie Zhao, Jinhui Guo, Zhenyu Gao, Qiuran Xu, Xiaoge Hu","doi":"10.1016/j.gene.2024.149134","DOIUrl":"10.1016/j.gene.2024.149134","url":null,"abstract":"<p><p>Gastric cancer (GC) has been ranked as the third incidence tumors globally. Long non-coding RNA (lncRNA) NRAV has been reported as a tumor-enhancer in the development of human cancers, whereas the function of NRAV in GC remains to be elucidated. The aim of this research was to explore the underlying function of NRAV in GC. Through comprehensive bioinformatics analysis, a significantly elevation of NRAV was found in both human GC tissues and cell lines, which indicated the poor prognosis of GC patients. Then, we conducted a series of functional experiments to illustrate the role of NRAV in GC. The results showed that the down-regulation of NRAV exhibited a significant inhibitory effect on GC cell proliferation and migration, while NRAV overexpression promoted GC cell proliferation and migration. Through xenograft mouse tumor model, the suppression of NRAV led to a reduction in the growth of tumor mice, whereas overexpression of NRAV notably enhanced tumor growth. Finally, EFHC1 was revealed as the potential target gene of NRAV. Overall, our findings indicated the promising application of NRAV as a therapeutic target and prognostic biomarker for GC.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149134"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767903","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}
GenePub Date : 2025-02-10Epub Date: 2024-11-28DOI: 10.1016/j.gene.2024.149124
Anaque O Pires, Louise C de Lima, Candace M de Andrade, Raísa S Coelho, Hátilla Dos S Silva, Gerson A Queiroz, Jamille Fernandes, Gabriela P Pinheiro, Álvaro A Cruz, Ryan Dos S Costa, Camila A V Figueiredo
{"title":"New variants of the DAD1 and OXA1L genes are associated with asthma and atopy in an adult population.","authors":"Anaque O Pires, Louise C de Lima, Candace M de Andrade, Raísa S Coelho, Hátilla Dos S Silva, Gerson A Queiroz, Jamille Fernandes, Gabriela P Pinheiro, Álvaro A Cruz, Ryan Dos S Costa, Camila A V Figueiredo","doi":"10.1016/j.gene.2024.149124","DOIUrl":"10.1016/j.gene.2024.149124","url":null,"abstract":"<p><p>Asthma is a complex disease characterized by reversible and intermittent airway obstruction that has shown a high prevalence and unacceptable mortality in adults. In recent years, several genome-wide association studies (GWAS) have identified variants linked to asthma susceptibility. The DAD1 gene is known for regulating programmed cell death, and OXA1L is described for its involvement in mitochondrial biogenesis and oxidative phosphorylation. The present study aimed to identify variants in the DAD1 and OXA1L genes and to evaluate the association with asthma and atopy markers in adults. 1,084 individuals were divided into mild to moderate asthma, severe asthma, and participants with no asthma (controls). Association analyses were performed using a multivariate logistic regression model adjusted for sex, age, body mass index (BMI), smoking, forced expiratory volume in 1 s (FEV1), and component ancestry master (PC1) using PLINK 1.9 software. This study identified new variants in the DAD1 and OXA1L genes that had never been described before. The C allele of rs200470407 in OXA1L was negatively associated with poor asthma control (OR: 0.32; p-value 0.049) and increased IL-13 (p-value < 0.0001). The alternative allele of rs1681577 was associated with severe asthma (OR: 2.23; p-value 0.01), pulmonary obstruction (OR: 4.12; p-value 0.046), and eosinophilia (OR: 2.42; p-value < 0.001). Our findings demonstrate that variants in the DAD1 and OXA1L genes are linked to asthma and atopy in Brazilian adults.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149124"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767946","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}
GenePub Date : 2025-02-10Epub Date: 2024-12-04DOI: 10.1016/j.gene.2024.149142
Huihuang Li, Yue Yang, Fan Yang, Xinguo Bao, Chengfu Pan, Weilong Lin, Lianjie Lai, Weimin Lin, Ruiyi Lin
{"title":"Determination of blood biochemical indices and research of egg quality-related candidate gene CDH5 in Putian black duck.","authors":"Huihuang Li, Yue Yang, Fan Yang, Xinguo Bao, Chengfu Pan, Weilong Lin, Lianjie Lai, Weimin Lin, Ruiyi Lin","doi":"10.1016/j.gene.2024.149142","DOIUrl":"10.1016/j.gene.2024.149142","url":null,"abstract":"<p><p>Improving egg quality and enhancing production efficiency are essential goals in poultry breeding. CDH5 encodes a cadherin involved in Ca<sup>2+</sup> transport in endothelial cells. The role of CDH5 in regulating duck egg quality and its mechanisms affecting Ca<sup>2+</sup> concentrations in duck uterine epithelial cells remains unclear. This study evaluated egg quality traits of the Putian black duck and conducted an association analysis with blood biochemical indices and single nucleotide polymorphisms in CDH5. Additionally, we constructed a CDH5 overexpression vector and synthesized specific siRNAs for transfection into Putian black duck uterine epithelial cells to assess Ca<sup>2+</sup> concentrations. Our results revealed a significant association between egg quality and five novel SNPs in CDH5, along with various blood biochemical indices. Further experiments demonstrated that CDH5 overexpression and knockdown reduced Ca<sup>2+</sup> concentrations in the uterine epithelial cells of Putian black ducks.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149142"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791494","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 SOX9-related prognostic DEGs and a prediction model for hepatitis C-induced early-stage fibrosis.","authors":"Haozheng Cai, Junyi Shen, Wei Peng, Xiaoyun Zhang, Tianfu Wen","doi":"10.1016/j.gene.2024.149133","DOIUrl":"10.1016/j.gene.2024.149133","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis C virus (HCV) infection induces liver inflammation, activating hepatic stellate cells (HSC) and advancing fibrosis. Studies have indicated that SOX9 overexpression is closely linked to HSC activation. The study aims to identify genes associated with SOX9 and search for potential targets for detecting and treating liver fibrosis.</p><p><strong>Method: </strong>The dataset GSE15654, containing 216 biopsy samples from HCV-induced early-stage cirrhosis patients, was obtained from the GEO database. Prognostic genes were identified through differential gene analysis, LASSO, and Cox regression analyses. CIBERSORT analysis quantified infiltration levels across 22 immune cell types. Constructing a prognostic prediction model using screened genes and conducting preliminary validation using qRT PCR and RNA sequencing techniques.</p><p><strong>Results: </strong>Elevated SOX9 expression correlates with unfavorable outcomes in patients with early-stage liver fibrosis induced by HCV. We identified nine SOX9-related prognostic DEGs in our study. ADAMTS2, ARHGEF5, CCT8, ERG, LBH, FRMD6, INMT, and RASGRF2 were considered risk factors in the disease progression, while DHRS4 was considered a protective factor. SOX9 expression showed a positive correlation with mast cell infiltration, whereas ARHGEF5 and FRMD6 expressions were positively associated with M0 macrophage infiltration. Our combined model surpasses the commonly used APRI and FIB4 indicators in predicting patient prognosis. The testing of clinical samples also preliminarily validated our research results.</p><p><strong>Conclusion: </strong>The prognostic model based on nine SOX9-related DEGs provides an effective tool for forecasting the progression and outcomes of liver fibrosis. This study introduces a new strategy for advancing liver fibrosis prediction and treatment.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149133"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767940","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}
GenePub Date : 2025-02-10Epub Date: 2024-12-06DOI: 10.1016/j.gene.2024.149154
Peizhi Yu, Xia Tang, Banglan Chen, Zihao Chen, Wenli Cui, Yuhang Xing, Ying Li, Fangfang Zhang, Juan B Barroso, Lucas Gutierrez Rodriguez, Yinan Yao, Yongfeng Gao
{"title":"The melatonin synthase-encoding gene ASMT mediates poplar resistance to drought stress and fungi Dothiorella gregaria.","authors":"Peizhi Yu, Xia Tang, Banglan Chen, Zihao Chen, Wenli Cui, Yuhang Xing, Ying Li, Fangfang Zhang, Juan B Barroso, Lucas Gutierrez Rodriguez, Yinan Yao, Yongfeng Gao","doi":"10.1016/j.gene.2024.149154","DOIUrl":"10.1016/j.gene.2024.149154","url":null,"abstract":"<p><p>In recent years, the increase in extreme climates, such as persistent high temperatures and drought, has adversely affected the growth and development of fast-growing trees. Melatonin (MT) plays an important role in plant responses to biotic and abiotic stresses, yet there is a lack of research on the specific role of limiting enzyme genes for MT biosynthesis in fast-growing woody plants. In this study, we investigated the function of PtoASMT, a key rate-limiting enzyme encoding gene for MT biosynthesis, which can be induced by drought, salt, and the phytohormones ABA, SA and JA. Our results show that: (1) PtoASMT was widely expressed in all tissues of poplar, but was highly expressed in petioles, moderately expressed in roots, stems, shoots and young leaves, exhibiting a typical diurnal expression rhythm in leaves, with the encoded protein localized on chloroplasts; (2) the content of MT was significantly promoted in overexpressing PtoASMT transgenic poplar plants, but there were no obvious differences in their growth and development; (3) overexpressing PtoASMT plants exhibited stronger drought tolerance, accumulating less reactive oxygen species (ROS) under drought stress relative to wild-type plants, whereas knockout PtoASMT plants were more sensitive and accumulated more ROS; (4) overexpressing PtoASMT plants were more resistant to fungi Dothiorella gregaria than WT plants, while knockout plants showed higher sensitivity; meanwhile, the expression of disease resistance-related genes (PRs and JAZ10) was significantly altered. We conclude that PtoASMT enhances the resistance of poplar to drought and Dothiorella gregaria by mediating MT biosynthesis in poplar. These findings contribute to a better understanding the role of ASMT gene in MT accumulation and stress resistance in poplar.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149154"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793938","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":"Comparative transcriptome analysis and transient assays revealed AaGST and AaBGAL, respectively, contribute to skin and flesh coloration in A. arguta.","authors":"Xu Zhan, Yukuo Li, Zhe Song, Xiaohan Li, Lingshuai Ye, Miaomiao Lin, Ran Wang, Leiming Sun, Jinbao Fang, Dixin Chen, Xiujuan Qi","doi":"10.1016/j.gene.2024.149143","DOIUrl":"10.1016/j.gene.2024.149143","url":null,"abstract":"<p><p>Actinidia arguta possesses different colors in the fruit skin and flesh, but the underlying mechanism has not yet been clarified. In this study, we conducted 36 samples RNA-seq to investigate the phenotypic expression of different fruit tissues (skin and flesh) in red and green A. arguta varieties during different coloring phases. GO and KEGG enrichment results of differentially expressed genes (DEGs) suggested that the red color of the skin and flesh was derived from anthocyanin transport and flesh softening, respectively. Weighted gene co-expression network analysis (WGCNA) revealed MEyellow and MEblack modules significantly correlated with skin and flesh coloration, and two genes, Glutathione S-transferases (AaGST) and β-galactosidases (AaBGAL), were identified as hub genes involved in different tissue-specific coloration. Transient overexpression in apples and kiwifruits confirmed the role of AaGST and AaBGAL in color formation. Our results preliminarily explore the mechanism of red color formation in different A. arguta fruit tissues and provide novel insights into red color formation.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149143"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791481","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":"miR-6760-5p suppresses neoangiogenesis by targeting Yes-associated protein 1 in patients with moyamoya disease undergoing indirect revascularization.","authors":"Yunyu Wen, Junda Chen, Tinghan Long, Fangzhou Chen, Zhibin Wang, Siyuan Chen, Guozhong Zhang, Mingzhou Li, Shichao Zhang, Huibin Kang, Wenfeng Feng, Gang Wang","doi":"10.1016/j.gene.2024.149152","DOIUrl":"10.1016/j.gene.2024.149152","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this research was to investigate the specific regulatory role of miR-6760-5p in angiogenesis in moyamoya disease.</p><p><strong>Methods: </strong>HUVECs were transfected with miR-6760-5p inhibitor and mimics fragments, then subjected to assays for cell proliferation, migration, and tube formation. Subsequently, downstream target genes of miR-6760-5p were predicted and the protein expression levels of these genes were evaluated. The presence of miR-6760-5p and YAP1 was verified by a dual luciferase reporter gene test, followed by an assessment of the effects of YAP1 and miR-6760-5p on the HUVECs.</p><p><strong>Results: </strong>Comparatively to the control group, increased expression of miR-6760-5p decreased cell growth, movement, and tube formation. YAP1 gene was discovered as a target controlled by miR-6760-5p, with subsequent investigation confirming YAP1 as a gene regulated by miR-6760-5p. Additionally, miR-6760-5p was found to counteract the angiogenesis-promoting effect of YAP1.</p><p><strong>Conclusion: </strong>The results of this research suggest a possible link between the miR-6760-5p gene found in the cerebrospinal fluid of individuals with moyamoya disease and the process of vascularization in this particular condition. The findings indicate that miR-6760-5p may be a new molecular indicator and potential target for the diagnosis of moyamoya disease.</p>","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149152"},"PeriodicalIF":2.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812817","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}