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Individual plant genetics reveal the control of local adaptation in European maize landraces. 单个植物遗传学揭示了欧洲玉米地方品种的地方适应控制。
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-05-21 DOI: 10.1186/s12915-025-02241-8
Leke Victor Aiyesa, Dietrich Kaufmann, Birgit Zumbach, Wolfgang Link, Stefan Scholten, Timothy Beissinger
{"title":"Individual plant genetics reveal the control of local adaptation in European maize landraces.","authors":"Leke Victor Aiyesa, Dietrich Kaufmann, Birgit Zumbach, Wolfgang Link, Stefan Scholten, Timothy Beissinger","doi":"10.1186/s12915-025-02241-8","DOIUrl":"10.1186/s12915-025-02241-8","url":null,"abstract":"<p><strong>Background: </strong>European maize landraces encompass a large amount of genetic diversity, allowing them to be well-adapted to their local environments. This diversity can be exploited to improve the fitness of elite material in the face of a changing climate.</p><p><strong>Results: </strong>We characterized the genetic diversity of 333 individual plants from 40 European maize landrace populations (EMLPs). We identified five genetic groups that mirrored the proximities of their geographical origins. Fixation indices showed moderate differentiation among genetic groups (0.034 to 0.093). More than half of the genetic variance was observed to be partitioned among individuals. Nucleotide diversity of EMLPs decreased significantly as latitude increased (from 0.16 to 0.04), suggesting serial founder events during maize expansion in Europe. GWAS with latitude, longitude, and elevation as response variables identified 28, 347, and 68 significant SNP positions, respectively. We pinpointed significant SNPs near dwarf8, tb1, ZCN7, ZCN8, and ZmMADS69 and identified 126 candidate genes with ontology terms indicative of local adaptation in maize, regulating adaptation to diverse abiotic and biotic environmental stresses.</p><p><strong>Conclusions: </strong>This study suggests a quick and cost-efficient approach to identifying genes involved in local adaptation without requiring field data. The EMLPs used in this study have been assembled to serve as a continuing resource of genetic diversity for further research aimed at improving agronomically relevant adaptation traits.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"138"},"PeriodicalIF":4.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118801","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}
引用次数: 0
Horizontal cell connectivity in the anchovy retina-a 3D electron microscopic study. 凤尾鱼视网膜水平细胞连通性的三维电子显微镜研究。
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-05-19 DOI: 10.1186/s12915-025-02242-7
Petra Guder, Max Scheungrab, Peter Kohnert, Georgios Kolyfetis, Gerhard Wanner, Martin Heß
{"title":"Horizontal cell connectivity in the anchovy retina-a 3D electron microscopic study.","authors":"Petra Guder, Max Scheungrab, Peter Kohnert, Georgios Kolyfetis, Gerhard Wanner, Martin Heß","doi":"10.1186/s12915-025-02242-7","DOIUrl":"10.1186/s12915-025-02242-7","url":null,"abstract":"<p><strong>Background: </strong>Block-face scanning electron microscopy has opened a new era of connectomics research, in which it is possible to make dense reconstructions of all cells in a clipping of a neuronal network, such as the retina, resolving synaptic contacts. Anchovies, exceptionally abundant marine teleosts, have retinae with regions for triple cone-based color vision and a region with specialized cone photoreceptors, so-called polycones, made of long and short cones with axially oriented outer segment lamellae for polarization contrast vision. This modality, discovered in the 1970s, is unique in vertebrates, but the neural wiring for contrast generation in deeper retinal layers is unknown so far.</p><p><strong>Results: </strong>To elucidate the retinal connectomics of the European anchovy Engraulis encrasicolus (Linnaeus, 1758), in a first project, we investigated the shapes and cone-specific wiring rules of 3 horizontal cell types using volume electron microscopy and subsequent computer-aided reconstruction: H1 cells contact both cone types of the polycone, H2 cells contact only the short cones, and H3 cells are exclusively connected to rods. In addition, a distinctive double band of Müller fibers and a layer of H1 axon terminals were structurally clarified.</p><p><strong>Conclusions: </strong>The findings suggest that (1) the monochromatic polarization contrast system based on fine structure specializations in the outer retina is connected to an inherited (bichromatic) color contrast mechanism in the inner retina, (2) the anchovy polycones arose from red (now long) and green (now short) cones, and (3) the blue single cones disappeared in the relevant retinal region.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"137"},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101433","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}
引用次数: 0
EnGCI: enhancing GPCR-compound interaction prediction via large molecular models and KAN network. 基于大分子模型和KAN网络的gpcr -化合物相互作用预测。
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-05-15 DOI: 10.1186/s12915-025-02238-3
Weihao Liu, Xiaoli Li, Bo Hang, Pu Wang
{"title":"EnGCI: enhancing GPCR-compound interaction prediction via large molecular models and KAN network.","authors":"Weihao Liu, Xiaoli Li, Bo Hang, Pu Wang","doi":"10.1186/s12915-025-02238-3","DOIUrl":"10.1186/s12915-025-02238-3","url":null,"abstract":"<p><strong>Background: </strong>Identifying GPCR-compound interactions (GCI) plays a significant role in drug discovery and chemogenomics. Machine learning, particularly deep learning, has become increasingly influential in this domain. Large molecular models, due to their ability to capture detailed structural and functional information, have shown promise in enhancing the predictive accuracy of downstream tasks. Consequently, exploring the performance of these models in GCI prediction, as well as evaluating their effectiveness when integrated with other deep learning models, has emerged as a compelling research area. This paper aims to investigate these challenges.</p><p><strong>Results: </strong>This study introduces EnGCI, a novel model comprising two distinct modules. The MSBM integrates a graph isomorphism network (GIN) and a convolutional neural network (CNN) to extract features from GPCRs and compounds, respectively. These features are then processed by a Kolmogorov-Arnold network (KAN) for decision-making. The LMMBM utilizes two large-scale pre-trained models to extract features from compounds and GPCRs, and subsequently, KAN is again employed for decision-making. Each module leverages different sources of multimodal information, and their fusion enhances the overall accuracy of GPCR-compound interaction (GCI) prediction. Evaluating the EnGCI model on a rigorously curated GCI dataset, we achieved an AUC of approximately 0.89, significantly outperforming current state-of-the-art benchmark models.</p><p><strong>Conclusions: </strong>The EnGCI model integrates two complementary modules: one that learns molecular features from scratch for the GPCR-compound interaction (GCI) prediction task, and another that extracts molecular features using pre-trained large molecular models. After further processing and integration, these multimodal information sources enable a more profound exploration and understanding of the complex interaction relationships between GPCRs and compounds. The EnGCI model offers a robust and efficient framework that enhances GCI predictive capabilities and has the potential to significantly contribute to GPCR drug discovery.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"136"},"PeriodicalIF":4.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076039","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}
引用次数: 0
Tyrosinase in melanoma inhibits anti-tumor activity of PD-1 deficient T cells. 黑色素瘤酪氨酸酶抑制PD-1缺陷T细胞的抗肿瘤活性。
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-05-15 DOI: 10.1186/s12915-025-02237-4
Rong Huang, Yingbin Wang, Haitao Teng, Mengjun Xu, Kexin He, Yingzhuo Shen, Guo Guo, Xinyu Feng, Tianhan Li, Binhui Zhou, Marc Bajenoff, Toby Lawrence, Yinming Liang, Liaoxun Lu, Lichen Zhang
{"title":"Tyrosinase in melanoma inhibits anti-tumor activity of PD-1 deficient T cells.","authors":"Rong Huang, Yingbin Wang, Haitao Teng, Mengjun Xu, Kexin He, Yingzhuo Shen, Guo Guo, Xinyu Feng, Tianhan Li, Binhui Zhou, Marc Bajenoff, Toby Lawrence, Yinming Liang, Liaoxun Lu, Lichen Zhang","doi":"10.1186/s12915-025-02237-4","DOIUrl":"10.1186/s12915-025-02237-4","url":null,"abstract":"<p><strong>Background: </strong>Melanoma is one of the most commonly diagnosed malignancies and serves as a model for studying immunotherapy. The B16 melanoma model, resembling human cold tumors that lack T cell infiltration and show minimal response to PD-1 blockade, is widely used for studying melanoma and its resistance to immunotherapy. Therefore, understanding the molecular basis that prevents T cell-mediated anti-tumor activity in B16 melanoma is of great significance.</p><p><strong>Results: </strong>In this study, we generated tyrosinase knockout B16 melanoma cells using CRISPR/Cas9 and discovered that tyrosinase in melanoma significantly inhibits the anti-tumor activity of T cells. Tyrosinase deficiency leads to a 3.80-fold increase in T-cell infiltration and enhances T-cell activation within the tumor. Single-cell RNA sequencing reveals an altered cold tumor immunophenotype in tyrosinase-deficient B16 melanoma. In wild-type mice, T cells in tyrosinase-deficient tumors express elevated levels of PD-1 and Foxp3. However, strikingly, in PD-1 deficient mice, the loss of tyrosinase in B16 melanoma unleashes the anti-tumor activity of PD-1 deficient T cells. This enhanced anti-tumor activity is explained by significantly increased tumor T cell infiltration accompanied by reduced frequencies of regulatory T cells in PD-1 knockout mice.</p><p><strong>Conclusions: </strong>These findings suggest that targeting tyrosinase could convert cold tumors into an immune-responsive state in vivo using murine models. Inhibiting tyrosinase could enhance the effectiveness of PD-1 blockade, offering a new approach for melanoma patients who fail in current PD-1 inhibitor treatment.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"135"},"PeriodicalIF":4.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076112","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}
引用次数: 0
Bio-informed synthesis of marine-sourced indole derivatives: suppressing gram-negative bacteria biofilm and virulence. 海洋来源吲哚衍生物的生物信息合成:抑制革兰氏阴性菌生物膜和毒力。
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-05-15 DOI: 10.1186/s12915-025-02234-7
Karina Golberg, Kamal Elouarzaki, Bat-El Kagan, Marilou Shagan, Netta Shemesh, Esti Kramarsky-Winter, Anat Ben-Zvi, Yaffa Mizrachi Nebenzahl, Robert S Marks, Ariel Kushmaro
{"title":"Bio-informed synthesis of marine-sourced indole derivatives: suppressing gram-negative bacteria biofilm and virulence.","authors":"Karina Golberg, Kamal Elouarzaki, Bat-El Kagan, Marilou Shagan, Netta Shemesh, Esti Kramarsky-Winter, Anat Ben-Zvi, Yaffa Mizrachi Nebenzahl, Robert S Marks, Ariel Kushmaro","doi":"10.1186/s12915-025-02234-7","DOIUrl":"https://doi.org/10.1186/s12915-025-02234-7","url":null,"abstract":"<p><p>Biofilms cling to surfaces to form complex architectures allowing their bacterial creators to acquire multidrug resistance and claiming countless lives worldwide. Therefore, finding novel compounds that affect virulence and biofilm-forming capacity of resistant pathogenic bacteria is imperative. Recently, we identified indole-based compounds that possess anti-biofilm properties in coral-associated bacteria. We succeeded in efficiently synthesizing two of these compounds, 1,1'-bisindole (NN) and 2,3-dihydro-2,2'-bisindole (DIV). They were found to attenuate biofilms of gram-negative bacterial pathogens, including Pseudomonas aeruginosa and Acinetobacter baumannii. Combining these compounds with the antibiotic tobramycin resulted in significant biofilm inhibition, particularly in the eradication of mature P. aeruginosa biofilms. Both of the bisindole derivatives, suppressed a number of bacterial virulence factors, reduced bacterial adhesion, and improved survival rates in infected Caenorhabditis elegans and human lung epithelial cell models. Transcriptome analyses of the bacteria treated with these compounds revealed that NN repressed or upregulated 307 genes when compared to untreated P. aeruginosa. These bacteria-derived molecules act in resistance-quenching and are potentially important candidates for inclusion in treatment protocols. The use of compounds that prevent the biofilm from accumulating the high cell densities critical to its structural and functional maintenance represents significant progress in the management of bacterial persistence. Therefore, a possible clinical implementation of these innovative compounds holds a promising future.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"134"},"PeriodicalIF":4.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076037","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}
引用次数: 0
Interpretable multi-instance heterogeneous graph network learning modelling CircRNA-drug sensitivity association prediction. 可解释的多实例异构图网络学习建模circrna -药物敏感性关联预测。
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-05-14 DOI: 10.1186/s12915-025-02223-w
Mengting Niu, Chunyu Wang, Yaojia Chen, Quan Zou, Ximei Luo
{"title":"Interpretable multi-instance heterogeneous graph network learning modelling CircRNA-drug sensitivity association prediction.","authors":"Mengting Niu, Chunyu Wang, Yaojia Chen, Quan Zou, Ximei Luo","doi":"10.1186/s12915-025-02223-w","DOIUrl":"https://doi.org/10.1186/s12915-025-02223-w","url":null,"abstract":"<p><strong>Background: </strong>Different expression levels of circular RNAs (circRNAs) affect the sensitivity of human cells to drugs, thus producing different responses to the therapeutic effects of drugs. Using traditional biomedical experiments to discover and confirm sensitivity relationships is not only time-consuming but also costly. Therefore, developing an effective method to accurately predict new associations between circRNAs and drug sensitivity is crucial and urgent. Therefore, we constructed a heterogeneous graph network MiGNN2CDS on the basis of multi-instance learning (MIL).</p><p><strong>Results: </strong>We first extracted similar features of circRNAs and drugs and the structural features of drugs to construct a heterogeneous network. To learn the deep embedding features of the heterogeneous network, we designed a heterogeneous graph convolutional network (GCN) architecture. By introducing instance learning, we subsequently designed a pseudo-metapath instance generator and a bidirectional translation embedding projector BiTrans to learn the metapath-level representation of circRNA-drug pairs. Finally, an interpretable multiscale attention network joint predictor was designed to achieve accurate prediction and interpretable analysis of circRNA-drug sensitivity associations.</p><p><strong>Conclusions: </strong>MiGNN2CDS achieves better prediction accuracy than many state-of-the-art models do. Case studies show that MiGNN2CDS can effectively predict unknown associations, and the model interpretability of MiGNN2CDS is verified by high-confidence meta-path analysis. The code and data are available at https://github.com/nmt315320/MiGNN2CDS.git .</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"131"},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076101","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}
引用次数: 0
Transcriptomic signatures of oxytosis/ferroptosis are enriched in Alzheimer's disease. 阿尔茨海默病中氧中毒/铁下垂的转录组特征丰富。
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-05-14 DOI: 10.1186/s12915-025-02235-6
Antonio Currais, Kayla Sanchez, David Soriano-Castell, Nawab John Dar, K Garrett Evensen, Salvador Soriano, Pamela Maher
{"title":"Transcriptomic signatures of oxytosis/ferroptosis are enriched in Alzheimer's disease.","authors":"Antonio Currais, Kayla Sanchez, David Soriano-Castell, Nawab John Dar, K Garrett Evensen, Salvador Soriano, Pamela Maher","doi":"10.1186/s12915-025-02235-6","DOIUrl":"https://doi.org/10.1186/s12915-025-02235-6","url":null,"abstract":"<p><strong>Background: </strong>Oxytosis/ferroptosis is a form of non-apoptotic regulated cell death characterized by specific changes in the redox balance that lead to lethal lipid peroxidation. It has been hypothesized recently that aging predisposes the brain to the activation of oxytosis/ferroptosis in Alzheimer's disease (AD), and consequently that inhibition of oxytosis/ferroptosis offers a path to develop a new class of therapeutics for the disease. The goal of the present study was to investigate the occurrence of oxytosis/ferroptosis in the AD brain by examining transcriptomic signatures of oxytosis/ferroptosis in cellular and animal models of AD as well as in human AD brain samples.</p><p><strong>Results: </strong>Since oxytosis/ferroptosis has been poorly defined at the RNA level, the publicly available datasets are limited. To address this limitation, we developed TrioSig, a gene signature generated from transcriptomic data of human microglia, astrocytes, and neurons treated with inducers of oxytosis/ferroptosis. It is shown that the different signatures of oxytosis/ferroptosis are enriched to varying extents in the brains of AD mice and human AD patients. The TrioSig signature was the most frequently found enriched, and bioinformatic analysis of its composition identified genes involved in the integrated stress response (ISR). It was confirmed in nerve cell culture that oxytosis/ferroptosis induces the ISR via phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and activating transcription factor 4 (ATF4) signaling.</p><p><strong>Conclusions: </strong>Our data support the involvement of oxytosis/ferroptosis in AD. The implications of the ISR for the progression and prevention of AD are discussed.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"132"},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076111","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}
引用次数: 0
A comprehensive evaluation of diversity measures for TCR repertoire profiling. TCR曲目分析的多样性措施的综合评价。
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-05-14 DOI: 10.1186/s12915-025-02236-5
Justyna Mika, Alicja Polanska, Kim Rm Blenman, Lajos Pusztai, Joanna Polanska, Serge Candéias, Michal Marczyk
{"title":"A comprehensive evaluation of diversity measures for TCR repertoire profiling.","authors":"Justyna Mika, Alicja Polanska, Kim Rm Blenman, Lajos Pusztai, Joanna Polanska, Serge Candéias, Michal Marczyk","doi":"10.1186/s12915-025-02236-5","DOIUrl":"https://doi.org/10.1186/s12915-025-02236-5","url":null,"abstract":"<p><strong>Background: </strong>T cells play a crucial role in adaptive immunity, as they monitor internal and external immunogenic signals through their specific receptors (TCRs). Using high-throughput sequencing, one can assess TCR repertoire in various clinical settings and describe it quantitatively by calculating a diversity index. Multiple diversity indices that capture the richness of TCRs and the evenness of their distribution have been proposed in the literature; however, there is no consensus on gold-standard measures and interpretation of each index is complex. Our goal was to examine the performance characteristics of 12 commonly used diversity indices in simulated and real-world data.</p><p><strong>Results: </strong>Simulated data were generated to evaluate how data richness and evenness affect index values using three nonparametric models. Fourteen real-world TCR datasets were obtained to examine differences in indices by analysis protocols and test their robustness to subsampling. Pielou, Basharin, d50, and Gini primarily describe evenness and highly correlate with one another. They are best suited for measuring the representation of TCR clones. Richness is best captured by S index, next Chao1 and ACE which also consider information on evenness. Shannon, Inv.Simspon, D3, D4, and Gini.Simpson measure richness and increasingly more information on evenness. More skewed TCR distributions provided more stable results in subsampling. Gini-Simpson, Pielou, and Basharin were the most robust in both simulated and experimental data.</p><p><strong>Conclusions: </strong>Our results could guide investigators to select the best diversity index for their particular experimental question and draw attention to factors that can influence the accuracy and reproducibility of results.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"133"},"PeriodicalIF":4.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076032","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}
引用次数: 0
Guanine quadruplexes mediate mitochondrial RNA polymerase pausing. 鸟嘌呤四聚体介导线粒体RNA聚合酶暂停。
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-05-13 DOI: 10.1186/s12915-025-02229-4
Ryan J Snyder, Uma Shankar, Don Delker, Winny Soerianto, Joshua T Burdick, Vivian G Cheung, Jason A Watts
{"title":"Guanine quadruplexes mediate mitochondrial RNA polymerase pausing.","authors":"Ryan J Snyder, Uma Shankar, Don Delker, Winny Soerianto, Joshua T Burdick, Vivian G Cheung, Jason A Watts","doi":"10.1186/s12915-025-02229-4","DOIUrl":"10.1186/s12915-025-02229-4","url":null,"abstract":"<p><strong>Background: </strong>The information content within nucleic acids extends beyond the primary sequence to include secondary structures with functional roles in transcription regulation. Guanine-rich sequences form structures called guanine quadruplexes that result from non-canonical base pairing between guanine residues. These stable guanine quadruplex structures are prevalent in gene promoters in nuclear DNA and are known to be associated with promoter proximal pausing of some genes. However, the transcriptional impact of guanine quadruplexes that form in nascent RNA is poorly understood.</p><p><strong>Results: </strong>We examined mitochondrial RNA polymerase (POLRMT) pausing patterns in primary human skin fibroblast cells using the precision nuclear run-on assay and uncovered over 400 pause sites on the mitochondrial genome. We identified that these pauses frequently occur following guanine-rich sequences where quadruplexes form. Using an in vitro primer extension assay, we show that quadruplexes formed in nascent RNA act as mediators of POLRMT pausing, and in cell-based assays their stabilization disrupts POLRMT transcription. Cells exposed to a guanine-quadruplex stabilizing agent (RHPS4) had diminished mitochondrial gene expression and significantly lowered cellular respiration within 24 h. The resulting ATP stress was sufficient to reduce active transport in renal epithelia.</p><p><strong>Conclusions: </strong>Our findings connect RNA guanine quadruplex-mediated pausing with the regulation of POLRMT transcription and mitochondrial function. We demonstrate that tuning of quadruplex dynamics in nascent RNA, rather than template DNA upstream of the polymerase, is sufficient to regulate mitochondrial gene expression.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"129"},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966185","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}
引用次数: 0
Admixture and selection offer insights for the conservation and breeding of Guyuan cattle. 混合和选择对固原牛的保护和育种具有重要意义。
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-05-13 DOI: 10.1186/s12915-025-02213-y
Shuang Liu, Huixuan Yan, Xue Feng, Xiaoyu Luo, Yang Lv, Chuzhao Lei, Ningbo Chen, Yun Ma
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