Pub Date : 2024-09-13DOI: 10.1186/s12915-024-02000-1
Xingzhuo Yang, Xianguo Zhao, Zhangwu Zhao, Juan Du
Diapause, a pivotal phase in the insect life cycle, enables survival during harsh environmental conditions. Unraveling the gene expression profiles of the diapause process helps uncover the molecular mechanisms that underlying diapause, which is crucial for understanding physiological adaptations. In this study, we utilize RNA-seq and Ribo-seq data to examine differentially expressed genes (DEGs) and translational efficiency during diapause of Asian corn borer (Ostrinia furnacalis, ACB). Our results unveil genes classified as “forwarded”, “exclusive”, “intensified”, or “buffered” during diapause, shedding light on their transcription and translation regulation patterns. Furthermore, we explore the landscape of lncRNAs (long non-coding RNAs) during diapause and identify differentially expressed lncRNAs, suggesting their roles in diapause regulation. Comparative analysis of different types of diapause in insects uncovers shared and unique KEGG pathways. While shared pathways highlight energy balance, exclusive pathways in the ACB larvae indicate insect-specific adaptations related to nutrient utilization and stress response. Interestingly, our study also reveals dynamic changes in the HSP70 gene family and proteasome pathway during diapause. Manipulating HSP protein levels and proteasome pathway by HSP activator or inhibitor and proteasome inhibitor affects diapause, indicating their vital role in the process. In summary, these findings enhance our knowledge of how insects navigate challenging conditions through intricate molecular mechanisms.
{"title":"Genome-wide analysis reveals transcriptional and translational changes during diapause of the Asian corn borer (Ostrinia furnacalis)","authors":"Xingzhuo Yang, Xianguo Zhao, Zhangwu Zhao, Juan Du","doi":"10.1186/s12915-024-02000-1","DOIUrl":"https://doi.org/10.1186/s12915-024-02000-1","url":null,"abstract":"Diapause, a pivotal phase in the insect life cycle, enables survival during harsh environmental conditions. Unraveling the gene expression profiles of the diapause process helps uncover the molecular mechanisms that underlying diapause, which is crucial for understanding physiological adaptations. In this study, we utilize RNA-seq and Ribo-seq data to examine differentially expressed genes (DEGs) and translational efficiency during diapause of Asian corn borer (Ostrinia furnacalis, ACB). Our results unveil genes classified as “forwarded”, “exclusive”, “intensified”, or “buffered” during diapause, shedding light on their transcription and translation regulation patterns. Furthermore, we explore the landscape of lncRNAs (long non-coding RNAs) during diapause and identify differentially expressed lncRNAs, suggesting their roles in diapause regulation. Comparative analysis of different types of diapause in insects uncovers shared and unique KEGG pathways. While shared pathways highlight energy balance, exclusive pathways in the ACB larvae indicate insect-specific adaptations related to nutrient utilization and stress response. Interestingly, our study also reveals dynamic changes in the HSP70 gene family and proteasome pathway during diapause. Manipulating HSP protein levels and proteasome pathway by HSP activator or inhibitor and proteasome inhibitor affects diapause, indicating their vital role in the process. In summary, these findings enhance our knowledge of how insects navigate challenging conditions through intricate molecular mechanisms.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223793","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}
Pub Date : 2024-09-12DOI: 10.1186/s12915-024-01970-6
Tess Cherlin, Yi Jing, Siddhartha Shah, Anne Kennedy, Aristeidis G. Telonis, Venetia Pliatsika, Haley Wilson, Lily Thompson, Panagiotis I. Vlantis, Phillipe Loher, Benjamin Leiby, Isidore Rigoutsos
MicroRNA isoforms (isomiRs), tRNA-derived fragments (tRFs), and rRNA-derived fragments (rRFs) represent most of the small non-coding RNAs (sncRNAs) found in cells. Members of these three classes modulate messenger RNA (mRNA) and protein abundance and are dysregulated in diseases. Experimental studies to date have assumed that the subcellular distribution of these molecules is well-understood, independent of cell type, and the same for all isoforms of a sncRNA. We tested these assumptions by investigating the subcellular distribution of isomiRs, tRFs, and rRFs in biological replicates from three cell lines from the same tissue and same-sex donors that model the same cancer subtype. In each cell line, we profiled the isomiRs, tRFs, and rRFs in the nucleus, cytoplasm, whole mitochondrion (MT), mitoplast (MP), and whole cell. Using a rigorous mathematical model we developed, we accounted for cross-fraction contamination and technical errors and adjusted the measured abundances accordingly. Analyses of the adjusted abundances show that isomiRs, tRFs, and rRFs exhibit complex patterns of subcellular distributions. These patterns depend on each sncRNA’s exact sequence and the cell type. Even in the same cell line, isoforms of the same sncRNA whose sequences differ by a few nucleotides (nts) can have different subcellular distributions. SncRNAs with similar sequences have different subcellular distributions within and across cell lines, suggesting that each isoform could have a different function. Future computational and experimental studies of isomiRs, tRFs, and rRFs will need to distinguish among each molecule’s various isoforms and account for differences in each isoform’s subcellular distribution in the cell line at hand. While the findings add to a growing body of evidence that isomiRs, tRFs, rRFs, tRNAs, and rRNAs follow complex intracellular trafficking rules, further investigation is needed to exclude alternative explanations for the observed subcellular distribution of sncRNAs.
{"title":"The subcellular distribution of miRNA isoforms, tRNA-derived fragments, and rRNA-derived fragments depends on nucleotide sequence and cell type","authors":"Tess Cherlin, Yi Jing, Siddhartha Shah, Anne Kennedy, Aristeidis G. Telonis, Venetia Pliatsika, Haley Wilson, Lily Thompson, Panagiotis I. Vlantis, Phillipe Loher, Benjamin Leiby, Isidore Rigoutsos","doi":"10.1186/s12915-024-01970-6","DOIUrl":"https://doi.org/10.1186/s12915-024-01970-6","url":null,"abstract":"MicroRNA isoforms (isomiRs), tRNA-derived fragments (tRFs), and rRNA-derived fragments (rRFs) represent most of the small non-coding RNAs (sncRNAs) found in cells. Members of these three classes modulate messenger RNA (mRNA) and protein abundance and are dysregulated in diseases. Experimental studies to date have assumed that the subcellular distribution of these molecules is well-understood, independent of cell type, and the same for all isoforms of a sncRNA. We tested these assumptions by investigating the subcellular distribution of isomiRs, tRFs, and rRFs in biological replicates from three cell lines from the same tissue and same-sex donors that model the same cancer subtype. In each cell line, we profiled the isomiRs, tRFs, and rRFs in the nucleus, cytoplasm, whole mitochondrion (MT), mitoplast (MP), and whole cell. Using a rigorous mathematical model we developed, we accounted for cross-fraction contamination and technical errors and adjusted the measured abundances accordingly. Analyses of the adjusted abundances show that isomiRs, tRFs, and rRFs exhibit complex patterns of subcellular distributions. These patterns depend on each sncRNA’s exact sequence and the cell type. Even in the same cell line, isoforms of the same sncRNA whose sequences differ by a few nucleotides (nts) can have different subcellular distributions. SncRNAs with similar sequences have different subcellular distributions within and across cell lines, suggesting that each isoform could have a different function. Future computational and experimental studies of isomiRs, tRFs, and rRFs will need to distinguish among each molecule’s various isoforms and account for differences in each isoform’s subcellular distribution in the cell line at hand. While the findings add to a growing body of evidence that isomiRs, tRFs, rRFs, tRNAs, and rRNAs follow complex intracellular trafficking rules, further investigation is needed to exclude alternative explanations for the observed subcellular distribution of sncRNAs.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223794","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}
Pub Date : 2024-09-11DOI: 10.1186/s12915-024-02005-w
Luca Peruzza, Francesco Cicala, Massimo Milan, Giulia Dalla Rovere, Tomaso Patarnello, Luciano Boffo, Morgan Smits, Silvia Iori, Angelo De Bortoli, Federica Schiavon, Aurelio Zentilin, Piero Fariselli, Barbara Cardazzo, Luca Bargelloni
Seafood is increasingly traded worldwide, but its supply chain is particularly prone to frauds. To increase consumer confidence, prevent illegal trade, and provide independent validation for eco-labelling, accurate tools for seafood traceability are needed. Here we show that the use of microbiome profiling (MP) coupled with machine learning (ML) allows precise tracing the origin of Manila clams harvested in areas separated by small geographic distances. The study was designed to represent a real-world scenario. Clams were collected in different seasons across the most important production area in Europe (lagoons along the northern Adriatic coast) to cover the known seasonal variation in microbiome composition for the species. DNA extracted from samples underwent the same depuration process as commercial products (i.e. at least 12 h in open flow systems). Machine learning-based analysis of microbiome profiles was carried out using two completely independent sets of data (collected at the same locations but in different years), one for training the algorithm, and the other for testing its accuracy and assessing the temporal stability signal. Briefly, gills (GI) and digestive gland (DG) of clams were collected in summer and winter over two different years (i.e. from 2018 to 2020) in one banned area and four farming sites. 16S DNA metabarcoding was performed on clam tissues and the obtained amplicon sequence variants (ASVs) table was used as input for ML MP. The best-predicting performances were obtained using the combined information of GI and DG (consensus analysis), showing a Cohen K-score > 0.95 when the target was the classification of samples collected from the banned area and those harvested at farming sites. Classification of the four different farming areas showed slightly lower accuracy with a 0.76 score. We show here that MP coupled with ML is an effective tool to trace the origin of shellfish products. The tool is extremely robust against seasonal and inter-annual variability, as well as product depuration, and is ready for implementation in routine assessment to prevent the trade of illegally harvested or mislabeled shellfish.
海产品在全球范围内的贸易量越来越大，但其供应链特别容易出现欺诈行为。为了增强消费者信心，防止非法贸易，并为生态标签提供独立验证，需要精确的海产品溯源工具。在这里，我们展示了微生物组图谱（MP）与机器学习（ML）的结合使用，可以精确追踪在地理距离较小的地区收获的马尼拉蛤蜊的来源。这项研究旨在反映真实世界的情况。在欧洲最重要的蛤蜊产地（亚得里亚海沿岸北部的泻湖）的不同季节采集蛤蜊，以涵盖该物种微生物组组成的已知季节性变化。从样本中提取的 DNA 经历了与商业产品相同的净化过程（即在开放式流动系统中至少 12 小时）。使用两组完全独立的数据（在相同地点但不同年份采集）对微生物组图谱进行了基于机器学习的分析，一组用于训练算法，另一组用于测试算法的准确性并评估时间稳定性信号。简言之，在一个禁渔区和四个养殖点，于两个不同年份（即从 2018 年到 2020 年）的夏季和冬季采集了蛤蜊的鳃（GI）和消化腺（DG）。对蛤蜊组织进行了 16S DNA 代谢编码，并将获得的扩增子序列变异（ASVs）表作为 ML MP 的输入。使用 GI 和 DG 的综合信息（共识分析）获得了最佳预测性能，当目标是对从禁渔区和养殖场采集的样本进行分类时，Cohen K 分数大于 0.95。四个不同养殖区的分类准确率略低，仅为 0.76 分。我们在此表明，MP 和 ML 是追踪贝类产品来源的有效工具。该工具对季节性、年际变化以及产品变质具有极高的稳定性，可用于常规评估，以防止非法捕捞或贴错标签的贝类产品的交易。
{"title":"Preventing illegal seafood trade using machine-learning assisted microbiome analysis","authors":"Luca Peruzza, Francesco Cicala, Massimo Milan, Giulia Dalla Rovere, Tomaso Patarnello, Luciano Boffo, Morgan Smits, Silvia Iori, Angelo De Bortoli, Federica Schiavon, Aurelio Zentilin, Piero Fariselli, Barbara Cardazzo, Luca Bargelloni","doi":"10.1186/s12915-024-02005-w","DOIUrl":"https://doi.org/10.1186/s12915-024-02005-w","url":null,"abstract":"Seafood is increasingly traded worldwide, but its supply chain is particularly prone to frauds. To increase consumer confidence, prevent illegal trade, and provide independent validation for eco-labelling, accurate tools for seafood traceability are needed. Here we show that the use of microbiome profiling (MP) coupled with machine learning (ML) allows precise tracing the origin of Manila clams harvested in areas separated by small geographic distances. The study was designed to represent a real-world scenario. Clams were collected in different seasons across the most important production area in Europe (lagoons along the northern Adriatic coast) to cover the known seasonal variation in microbiome composition for the species. DNA extracted from samples underwent the same depuration process as commercial products (i.e. at least 12 h in open flow systems). Machine learning-based analysis of microbiome profiles was carried out using two completely independent sets of data (collected at the same locations but in different years), one for training the algorithm, and the other for testing its accuracy and assessing the temporal stability signal. Briefly, gills (GI) and digestive gland (DG) of clams were collected in summer and winter over two different years (i.e. from 2018 to 2020) in one banned area and four farming sites. 16S DNA metabarcoding was performed on clam tissues and the obtained amplicon sequence variants (ASVs) table was used as input for ML MP. The best-predicting performances were obtained using the combined information of GI and DG (consensus analysis), showing a Cohen K-score > 0.95 when the target was the classification of samples collected from the banned area and those harvested at farming sites. Classification of the four different farming areas showed slightly lower accuracy with a 0.76 score. We show here that MP coupled with ML is an effective tool to trace the origin of shellfish products. The tool is extremely robust against seasonal and inter-annual variability, as well as product depuration, and is ready for implementation in routine assessment to prevent the trade of illegally harvested or mislabeled shellfish.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182141","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}
N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.
{"title":"The m6A writer KIAA1429 regulates photoaging progression via MFAP4-dependent collagen synthesis","authors":"Yuanyuan Liu, Jian Li, Chenhui Wang, Jiangbo Li, Kai Luo, Kang Tao, Yuan Tian, Xiang Song, Zhifang Zhai, Yuandong Tao, Jia You, Lihua Wu, Wenqian Li, Yuanyuan Jiao, Rongya Yang, Mingwang Zhang","doi":"10.1186/s12915-024-01976-0","DOIUrl":"https://doi.org/10.1186/s12915-024-01976-0","url":null,"abstract":"N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182026","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}
Kiwifruit, belonging to the genus Actinidia, represents a unique fruit crop characterized by its modern cultivars being genetically diverse and exhibiting remarkable variations in morphological traits and adaptability to harsh environments. However, the genetic mechanisms underlying such morphological diversity remain largely elusive. We report the high-quality genomes of five Actinidia species, including Actinidia longicarpa, A. macrosperma, A. polygama, A. reticulata, and A. rufa. Through comparative genomics analyses, we identified three whole genome duplication events shared by the Actinidia genus and uncovered rapidly evolving gene families implicated in the development of characteristic kiwifruit traits, including vitamin C (VC) content and fruit hairiness. A range of structural variations were identified, potentially contributing to the phenotypic diversity in kiwifruit. Notably, phylogenomic analyses revealed 76 cis-regulatory elements within the Actinidia genus, predominantly associated with stress responses, metabolic processes, and development. Among these, five motifs did not exhibit similarity to known plant motifs, suggesting the presence of possible novel cis-regulatory elements in kiwifruit. Construction of a pan-genome encompassing the nine Actinidia species facilitated the identification of gene DTZ79_23g14810 specific to species exhibiting extraordinarily high VC content. Expression of DTZ79_23g14810 is significantly correlated with the dynamics of VC concentration, and its overexpression in the transgenic roots of kiwifruit plants resulted in increased VC content. Collectively, the genomes and pan-genome of diverse Actinidia species not only enhance our understanding of fruit development but also provide a valuable genomic resource for facilitating the genome-based breeding of kiwifruit.
{"title":"Genomes of diverse Actinidia species provide insights into cis-regulatory motifs and genes associated with critical traits","authors":"Xiaolong Li, Liuqing Huo, Xinyi Li, Chaofan Zhang, Miaofeng Gu, Jialu Fan, Changbin Xu, Jinli Gong, Xiaoli Hu, Yi Zheng, Xuepeng Sun","doi":"10.1186/s12915-024-02002-z","DOIUrl":"https://doi.org/10.1186/s12915-024-02002-z","url":null,"abstract":"Kiwifruit, belonging to the genus Actinidia, represents a unique fruit crop characterized by its modern cultivars being genetically diverse and exhibiting remarkable variations in morphological traits and adaptability to harsh environments. However, the genetic mechanisms underlying such morphological diversity remain largely elusive. We report the high-quality genomes of five Actinidia species, including Actinidia longicarpa, A. macrosperma, A. polygama, A. reticulata, and A. rufa. Through comparative genomics analyses, we identified three whole genome duplication events shared by the Actinidia genus and uncovered rapidly evolving gene families implicated in the development of characteristic kiwifruit traits, including vitamin C (VC) content and fruit hairiness. A range of structural variations were identified, potentially contributing to the phenotypic diversity in kiwifruit. Notably, phylogenomic analyses revealed 76 cis-regulatory elements within the Actinidia genus, predominantly associated with stress responses, metabolic processes, and development. Among these, five motifs did not exhibit similarity to known plant motifs, suggesting the presence of possible novel cis-regulatory elements in kiwifruit. Construction of a pan-genome encompassing the nine Actinidia species facilitated the identification of gene DTZ79_23g14810 specific to species exhibiting extraordinarily high VC content. Expression of DTZ79_23g14810 is significantly correlated with the dynamics of VC concentration, and its overexpression in the transgenic roots of kiwifruit plants resulted in increased VC content. Collectively, the genomes and pan-genome of diverse Actinidia species not only enhance our understanding of fruit development but also provide a valuable genomic resource for facilitating the genome-based breeding of kiwifruit.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182020","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}
DNA G-quadruplexes (G4s) represent a distinctive class of non-canonical DNA secondary structures. Despite their recognition as potential therapeutic targets in some cancers, the developmental role of G4 structures remains enigmatic. Mammalian embryonic myogenesis studies are hindered by limitations, prompting the use of chicken embryo-derived myoblasts as a model to explore G4 dynamics. This study aims to reveal the embryonic G4s landscape and elucidate the underlying mechanisms for candidate G4s that influence embryonic myogenesis. This investigation unveils a significant reduction in G4s abundance during myogenesis. G4s stabilizer pyridostatin impedes embryonic myogenesis, emphasizing the regulatory role of G4s in this process. G4 Cut&Tag sequencing and RNA-seq analyses identify potential G4s and DEGs influencing embryonic myogenesis. Integration of G4 and DEG candidates identifies 32 G4s located in promoter regions capable of modulating gene transcription. WGBS elucidates DNA methylation dynamics during embryonic myogenesis. Coordinating transcriptome data with DNA G4s and DNA methylation profiles constructs a G4-DMR-DEG network, revealing nine interaction pairs. Notably, the NFATC2 promoter region sequence is confirmed to form a G4 structure, reducing promoter mCpG content and upregulating NFATC2 transcriptional activity. This comprehensive study unravels the first embryonic genomic G4s landscape, highlighting the regulatory role of NFATC2 G4 in orchestrating transcriptional activity through promoter DNA methylation during myogenesis.
DNA G-四重结构（G4s）是一类独特的非经典 DNA 二级结构。尽管它们被认为是某些癌症的潜在治疗靶点，但 G4 结构在发育过程中的作用仍然是个谜。哺乳动物胚胎肌生成研究受到诸多限制，这促使人们使用鸡胚胎衍生的肌母细胞作为模型来探索 G4 动态。本研究旨在揭示胚胎 G4s 格局，并阐明影响胚胎肌发生的候选 G4s 的潜在机制。这项研究揭示了在肌形成过程中 G4s 丰度的显著降低。G4s稳定剂哒哒司他汀阻碍了胚胎肌生成，强调了G4s在这一过程中的调控作用。G4 Cut&Tag 测序和 RNA-seq 分析确定了影响胚胎肌形成的潜在 G4s 和 DEGs。将 G4 和 DEG 候选者整合在一起，发现了 32 个位于启动子区域、能够调节基因转录的 G4s。WGBS阐明了胚胎肌肉发生过程中的DNA甲基化动态。将转录组数据与 DNA G4s 和 DNA 甲基化图谱相协调，构建了一个 G4-DMR-DEG 网络，揭示了九对相互作用。值得注意的是，NFATC2 启动子区域序列被证实形成了 G4 结构，减少了启动子 mCpG 含量并上调了 NFATC2 的转录活性。这项全面的研究首次揭示了胚胎基因组 G4s 图谱，凸显了 NFATC2 G4 在肌形成过程中通过启动子 DNA 甲基化协调转录活性的调控作用。
{"title":"The first embryonic landscape of G-quadruplexes related to myogenesis","authors":"Lijin Guo, Weiling Huang, Qi Wen, Siyu Zhang, Farhad Bordbar, Zhengzhong Xiao, Qinghua Nie","doi":"10.1186/s12915-024-01993-z","DOIUrl":"https://doi.org/10.1186/s12915-024-01993-z","url":null,"abstract":"DNA G-quadruplexes (G4s) represent a distinctive class of non-canonical DNA secondary structures. Despite their recognition as potential therapeutic targets in some cancers, the developmental role of G4 structures remains enigmatic. Mammalian embryonic myogenesis studies are hindered by limitations, prompting the use of chicken embryo-derived myoblasts as a model to explore G4 dynamics. This study aims to reveal the embryonic G4s landscape and elucidate the underlying mechanisms for candidate G4s that influence embryonic myogenesis. This investigation unveils a significant reduction in G4s abundance during myogenesis. G4s stabilizer pyridostatin impedes embryonic myogenesis, emphasizing the regulatory role of G4s in this process. G4 Cut&Tag sequencing and RNA-seq analyses identify potential G4s and DEGs influencing embryonic myogenesis. Integration of G4 and DEG candidates identifies 32 G4s located in promoter regions capable of modulating gene transcription. WGBS elucidates DNA methylation dynamics during embryonic myogenesis. Coordinating transcriptome data with DNA G4s and DNA methylation profiles constructs a G4-DMR-DEG network, revealing nine interaction pairs. Notably, the NFATC2 promoter region sequence is confirmed to form a G4 structure, reducing promoter mCpG content and upregulating NFATC2 transcriptional activity. This comprehensive study unravels the first embryonic genomic G4s landscape, highlighting the regulatory role of NFATC2 G4 in orchestrating transcriptional activity through promoter DNA methylation during myogenesis.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182060","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}
Pub Date : 2024-09-11DOI: 10.1186/s12915-024-02006-9
Si-Rui Xiao, Yao-Kun Zhang, Kai-Yu Liu, Yu-Xiang Huang, Rong Liu
Mutations occurring in nucleic acids or proteins may affect the binding affinities of protein-nucleic acid interactions. Although many efforts have been devoted to the impact of protein mutations, few computational studies have addressed the effect of nucleic acid mutations and explored whether the identical methodology could be applied to the prediction of binding affinity changes caused by these two mutation types. Here, we developed a generalized algorithm named PNBACE for both DNA and protein mutations. We first demonstrated that DNA mutations could induce varying degrees of changes in binding affinity from multiple perspectives. We then designed a group of energy-based topological features based on different energy networks, which were combined with our previous partition-based energy features to construct individual prediction models through feature selections. Furthermore, we created an ensemble model by integrating the outputs of individual models using a differential evolution algorithm. In addition to predicting the impact of single-point mutations, PNBACE could predict the influence of multiple-point mutations and identify mutations significantly reducing binding affinities. Extensive comparisons indicated that PNBACE largely performed better than existing methods on both regression and classification tasks. PNBACE is an effective method for estimating the binding affinity changes of protein-nucleic acid complexes induced by DNA or protein mutations, therefore improving our understanding of the interactions between proteins and DNA/RNA.
核酸或蛋白质中发生的突变可能会影响蛋白质-核酸相互作用的结合亲和力。尽管很多人致力于研究蛋白质突变的影响，但很少有计算研究涉及核酸突变的影响，并探讨是否可以将相同的方法应用于预测这两种突变类型引起的结合亲和力变化。在此，我们开发了一种名为 PNBACE 的通用算法，同时适用于 DNA 和蛋白质突变。我们首先从多个角度证明了 DNA 突变会引起不同程度的结合亲和力变化。然后，我们根据不同的能量网络设计了一组基于能量的拓扑特征，并将其与之前基于分区的能量特征相结合，通过特征选择构建了个体预测模型。此外，我们还利用差分进化算法整合了各个模型的输出结果，从而创建了一个集合模型。除了预测单点突变的影响外，PNBACE 还能预测多点突变的影响，并识别显著降低结合亲和力的突变。广泛的比较表明，在回归和分类任务中，PNBACE 的表现在很大程度上优于现有方法。PNBACE 是一种估算 DNA 或蛋白质突变引起的蛋白质-核酸复合物结合亲和力变化的有效方法，从而提高了我们对蛋白质与 DNA/RNA 之间相互作用的理解。
{"title":"PNBACE: an ensemble algorithm to predict the effects of mutations on protein-nucleic acid binding affinity","authors":"Si-Rui Xiao, Yao-Kun Zhang, Kai-Yu Liu, Yu-Xiang Huang, Rong Liu","doi":"10.1186/s12915-024-02006-9","DOIUrl":"https://doi.org/10.1186/s12915-024-02006-9","url":null,"abstract":"Mutations occurring in nucleic acids or proteins may affect the binding affinities of protein-nucleic acid interactions. Although many efforts have been devoted to the impact of protein mutations, few computational studies have addressed the effect of nucleic acid mutations and explored whether the identical methodology could be applied to the prediction of binding affinity changes caused by these two mutation types. Here, we developed a generalized algorithm named PNBACE for both DNA and protein mutations. We first demonstrated that DNA mutations could induce varying degrees of changes in binding affinity from multiple perspectives. We then designed a group of energy-based topological features based on different energy networks, which were combined with our previous partition-based energy features to construct individual prediction models through feature selections. Furthermore, we created an ensemble model by integrating the outputs of individual models using a differential evolution algorithm. In addition to predicting the impact of single-point mutations, PNBACE could predict the influence of multiple-point mutations and identify mutations significantly reducing binding affinities. Extensive comparisons indicated that PNBACE largely performed better than existing methods on both regression and classification tasks. PNBACE is an effective method for estimating the binding affinity changes of protein-nucleic acid complexes induced by DNA or protein mutations, therefore improving our understanding of the interactions between proteins and DNA/RNA.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182140","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}
Pub Date : 2024-09-11DOI: 10.1186/s12915-024-02004-x
Jinyu Zhu, Jingheng Chen, Yiran Liu, Xuejiao Xu, Jackson Champer
Methods to suppress pest insect populations using genetic constructs and repeated releases of male homozygotes have recently been shown to be an attractive alternative to older sterile insect techniques based on radiation. Female-specific lethal alleles have substantially increased power, but still require large, sustained transgenic insect releases. Gene drive alleles bias their own inheritance to spread throughout populations, potentially allowing population suppression with a single, small-size release. However, suppression drives often suffer from efficiency issues, and the most well-studied type, homing drives, tend to spread without limit. In this study, we show that coupling female-specific lethal alleles with homing gene drive allowed substantial improvement in efficiency while still retaining the self-limiting nature (and thus confinement) of a lethal allele strategy. Using a mosquito model, we show the required release sizes for population elimination in a variety of scenarios, including different density growth curves, with comparisons to other systems. Resistance alleles reduced the power of this method, but these could be overcome by targeting an essential gene with the drive while also providing rescue. A proof-of-principle demonstration of this system in Drosophila melanogaster was effective in both biasing its inheritance and achieving high lethality among females that inherit the construct in the absence of antibiotic. Overall, our study shows that substantial improvements can be achieved in female-specific lethal systems for population suppression by combining them with various types of gene drive.
{"title":"Population suppression with dominant female-lethal alleles is boosted by homing gene drive","authors":"Jinyu Zhu, Jingheng Chen, Yiran Liu, Xuejiao Xu, Jackson Champer","doi":"10.1186/s12915-024-02004-x","DOIUrl":"https://doi.org/10.1186/s12915-024-02004-x","url":null,"abstract":"Methods to suppress pest insect populations using genetic constructs and repeated releases of male homozygotes have recently been shown to be an attractive alternative to older sterile insect techniques based on radiation. Female-specific lethal alleles have substantially increased power, but still require large, sustained transgenic insect releases. Gene drive alleles bias their own inheritance to spread throughout populations, potentially allowing population suppression with a single, small-size release. However, suppression drives often suffer from efficiency issues, and the most well-studied type, homing drives, tend to spread without limit. In this study, we show that coupling female-specific lethal alleles with homing gene drive allowed substantial improvement in efficiency while still retaining the self-limiting nature (and thus confinement) of a lethal allele strategy. Using a mosquito model, we show the required release sizes for population elimination in a variety of scenarios, including different density growth curves, with comparisons to other systems. Resistance alleles reduced the power of this method, but these could be overcome by targeting an essential gene with the drive while also providing rescue. A proof-of-principle demonstration of this system in Drosophila melanogaster was effective in both biasing its inheritance and achieving high lethality among females that inherit the construct in the absence of antibiotic. Overall, our study shows that substantial improvements can be achieved in female-specific lethal systems for population suppression by combining them with various types of gene drive.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182142","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}
The molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge. Here, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including Pclo in dental follicle cells, Wnt10a in pre-odontoblasts, Fst and Igfbp2 in periodontal ligament cells, and validated the expression of Igfbp3 in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes Ptn and Satb2, while dental follicle cell differentiation is associated with the genes Tnc, Vim, Slc26a7, and Fgfr1. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene TNC was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar. Our results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration.
{"title":"Single-cell RNA-seq analysis of rat molars reveals cell identity and driver genes associated with dental mesenchymal cell differentiation","authors":"Yingchun Zheng, Ting Lu, Leitao Zhang, Zhongzhi Gan, Aoxi Li, Chuandong He, Fei He, Sha He, Jian Zhang, Fu Xiong","doi":"10.1186/s12915-024-01996-w","DOIUrl":"https://doi.org/10.1186/s12915-024-01996-w","url":null,"abstract":"The molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge. Here, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including Pclo in dental follicle cells, Wnt10a in pre-odontoblasts, Fst and Igfbp2 in periodontal ligament cells, and validated the expression of Igfbp3 in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes Ptn and Satb2, while dental follicle cell differentiation is associated with the genes Tnc, Vim, Slc26a7, and Fgfr1. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene TNC was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar. Our results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182022","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}
Fusarium head blight (FHB) significantly impacts wheat yield and quality. Understanding the intricate interaction mechanisms between Fusarium graminearum (the main pathogen of FHB) and wheat is crucial for developing effective strategies to manage and this disease. Our previous studies had shown that the absence of the cell wall mannoprotein FgCWM1, located at the outermost layer of the cell wall, led to a decrease in the pathogenicity of F. graminearum and induced the accumulation of salicylic acid (SA) in wheat. Hence, we propose that FgCWM1 may play a role in interacting between F. graminearum and wheat, as its physical location facilitates interaction effects. In this study, we have identified that the C-terminal region of NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 (NDUFA9) could interact with FgCWM1 through the yeast two-hybrid assay. The interaction was further confirmed through the combination of Co-IP and BiFC analyses. Consistently, the results of subcellular localization indicated that TaNDUFA9 was localized in the cytoplasm adjacent to the cell membrane and chloroplasts. The protein was also detected to be associated with mitochondria and positively regulated complex I activity. The loss-of-function mutant of TaNDUFA9 exhibited a delay in flowering, decreased seed setting rate, and reduced pollen fertility. However, it exhibited elevated levels of SA and increased resistance to FHB caused by F. graminearum infection. Meanwhile, inoculation with the FgCWM1 deletion mutant strain led to increased synthesis of SA in wheat. These findings suggest that TaNDUFA9 inhibits SA synthesis and FHB resistance in wheat. FgCWM1 enhances this inhibition by interacting with the C-terminal region of TaNDUFA9, ultimately facilitating F. graminearum infection in wheat. This study provides new insights into the interaction mechanism between F. graminearum and wheat. TaNDUFA9 could serve as a target gene for enhancing wheat resistance to FHB.
镰孢菌纹枯病（FHB）严重影响小麦的产量和品质。了解禾本科镰刀菌（FHB 的主要病原体）与小麦之间错综复杂的相互作用机制，对于制定有效的防治策略至关重要。我们之前的研究表明，位于细胞壁最外层的细胞壁甘露蛋白 FgCWM1 的缺失会降低禾谷镰孢的致病性，并诱导水杨酸（SA）在小麦中的积累。因此，我们认为 FgCWM1 可能在禾谷镰孢和小麦之间的相互作用中发挥作用，因为它的物理位置有利于产生相互作用效应。在本研究中，我们通过酵母双杂交试验发现 NADH 脱氢酶 [泛醌] 1 α 亚复合体亚基 9（NDUFA9）的 C 端区域可与 FgCWM1 相互作用。通过 Co-IP 和 BiFC 分析进一步证实了这种相互作用。亚细胞定位的结果一致表明，TaNDUFA9 定位于细胞质中细胞膜和叶绿体附近。还检测到该蛋白与线粒体相关，并对复合体 I 的活性有正向调节作用。TaNDUFA9 功能缺失突变体表现出开花延迟、结实率降低和花粉育性降低。但是，它的 SA 水平升高，对禾谷镰孢引起的 FHB 的抗性增强。同时，接种 FgCWM1 基因缺失突变株会增加小麦体内 SA 的合成。这些发现表明，TaNDUFA9 会抑制小麦的 SA 合成和 FHB 抗性。FgCWM1 通过与 TaNDUFA9 的 C 端区域相互作用，增强了这种抑制作用，最终促进了 F. graminearum 在小麦中的感染。这项研究为了解禾谷粉镰孢与小麦之间的相互作用机制提供了新的视角。TaNDUFA9可作为增强小麦抗FHB能力的靶基因。
{"title":"FgCWM1 modulates TaNDUFA9 to inhibit SA synthesis and reduce FHB resistance in wheat","authors":"Yazhou Zhang, Danyu Yao, Xinyu Yu, Xinyao Cheng, Lan Wen, Caihong Liu, Qiang Xu, Mei Deng, Qiantao Jiang, Pengfei Qi, Yuming Wei","doi":"10.1186/s12915-024-02007-8","DOIUrl":"https://doi.org/10.1186/s12915-024-02007-8","url":null,"abstract":"Fusarium head blight (FHB) significantly impacts wheat yield and quality. Understanding the intricate interaction mechanisms between Fusarium graminearum (the main pathogen of FHB) and wheat is crucial for developing effective strategies to manage and this disease. Our previous studies had shown that the absence of the cell wall mannoprotein FgCWM1, located at the outermost layer of the cell wall, led to a decrease in the pathogenicity of F. graminearum and induced the accumulation of salicylic acid (SA) in wheat. Hence, we propose that FgCWM1 may play a role in interacting between F. graminearum and wheat, as its physical location facilitates interaction effects. In this study, we have identified that the C-terminal region of NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 (NDUFA9) could interact with FgCWM1 through the yeast two-hybrid assay. The interaction was further confirmed through the combination of Co-IP and BiFC analyses. Consistently, the results of subcellular localization indicated that TaNDUFA9 was localized in the cytoplasm adjacent to the cell membrane and chloroplasts. The protein was also detected to be associated with mitochondria and positively regulated complex I activity. The loss-of-function mutant of TaNDUFA9 exhibited a delay in flowering, decreased seed setting rate, and reduced pollen fertility. However, it exhibited elevated levels of SA and increased resistance to FHB caused by F. graminearum infection. Meanwhile, inoculation with the FgCWM1 deletion mutant strain led to increased synthesis of SA in wheat. These findings suggest that TaNDUFA9 inhibits SA synthesis and FHB resistance in wheat. FgCWM1 enhances this inhibition by interacting with the C-terminal region of TaNDUFA9, ultimately facilitating F. graminearum infection in wheat. This study provides new insights into the interaction mechanism between F. graminearum and wheat. TaNDUFA9 could serve as a target gene for enhancing wheat resistance to FHB.","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223795","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}
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