BMC Biology最新文献

{"title":"Another tail of two sites: activation of the Notch ligand Delta by Mindbomb1.","authors":"Nicole Vüllings, Alina Airich, Ekaterina Seib, Tobias Troost, Thomas Klein","doi":"10.1186/s12915-025-02162-6","DOIUrl":"10.1186/s12915-025-02162-6","url":null,"abstract":"<p><strong>Background: </strong>Notch signalling plays a crucial role in many developmental, homoeostatic and pathological processes in metazoans. The pathway is activated by binding of the ligand to the Notch receptor, which changes the conformation of the receptor by exerting a pulling force. The pulling force is generated by the endocytosis of the interacting ligand into the signal-sending cell. Endocytosis of ligands requires the action of the E3 ligases Mindbomb1 (Mib1) and Neuralized (Neur) that ubiquitylate lysines (Ks) of their intracellular domains. It has been shown that human MIB1 binds JAGGED1 (JAG1) via a bipartite binding motif in its ICD. This interaction is required for the activation of JAG1. However, it is not known whether this bipartite binding mode is of general importance. It is also not rigorously tested whether it occurs in vivo. Moreover, it is not known whether Mib1 ubiquitylates specific Ks in the ICD of ligands, or is rather non-selective.</p><p><strong>Results: </strong>We therefore investigated how Mib1 interacts with the Notch ligand Delta of Drosophila in an in vivo trans-activation assay and determined the Ks which are required for signalling. We show that the activation of Dl by Mib1 follows similar rules as has been found for mammalian MIB1 and JAG1. We present evidence that a combination of six Ks of the ICD is required for the full signalling activity of Dl by Mib1, with K742 being the most important one.</p><p><strong>Conclusions: </strong>Altogether, our analysis further reveals the rules of Mib1-mediated DSL-ligand-dependent Notch-signalling.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"71"},"PeriodicalIF":4.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572137","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":"The circular RNA circbabo(5,6,7,8S) regulates lipid metabolism and neuronal integrity via TGF-β/ROS/JNK/SREBP signaling axis in Drosophila.","authors":"Jie Sheng, Xuemei Zhang, Weihong Liang, Junfang Lyu, Bei Zhang, Jie Min, Austin Xu, Xingyu Xu, Jennifer W Li, Jian-Liang Li, Rui Zhou, Wei Liu","doi":"10.1186/s12915-025-02175-1","DOIUrl":"10.1186/s12915-025-02175-1","url":null,"abstract":"<p><strong>Background: </strong>Lipid droplets (LDs) are dynamic cytoplasmic lipid-storing organelles that play a pivotal role in maintaining cellular energy balance, lipid homeostasis, and metabolic signaling. Dysregulation of lipid metabolism, particularly excessive lipogenesis, contributes to the abnormal accumulation of LDs in the nervous system, which is associated with several neurodegenerative diseases. Circular RNAs (circRNAs) are a new class of non-coding and regulatory RNAs that are widely expressed in eukaryotes. However, only a subset has been functionally characterized. Here, we identified and functionally characterized a new circular RNA circbabo(5,6,7,8S) that regulates lipogenesis and neuronal integrity in Drosophila melanogaster.</p><p><strong>Results: </strong>circbabo(5,6,7,8S) is derived from the babo locus which encodes the type I receptor for transforming growth factor β (TGF-β). Depletion of circbabo(5,6,7,8S) in flies causes elevated lipid droplet accumulation, progressive photoreceptor cell loss and shortened lifespan, phenotypes that are rescued by restoring circbabo(5,6,7,8S) expression. In addition, RNA-seq and epistasis analyses reveal that these abnormalities are caused by aberrant activation of the SREBP signaling pathway. Furthermore, circbabo(5,6,7,8S)-depleted tissues display enhanced activation of the TGF-β signaling pathway and compromised mitochondrial function, resulting in upregulation of reactive oxygen species (ROS). Moreover, we provide evidence that circbabo(5,6,7,8S) encodes the protein circbabo(5,6,7,8S)-p, which inhibits TGF-β signaling by interfering with the assembly of babo/put receptor heterodimer complex. Lastly, we show that dysregulation of the ROS/JNK/SREBP signaling cascade is responsible for the LD accumulation, neurodegeneration, and shortened lifespan phenotypes elicited by circbabo(5,6,7,8S) depletion.</p><p><strong>Conclusions: </strong>Our study demonstrates the physiological role of the protein-coding circRNA circbabo(5,6,7,8S) in regulating lipid metabolism and neuronal integrity.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"69"},"PeriodicalIF":4.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555948","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":"The interplay between epigenomic and transcriptomic variation during ecotype divergence in stickleback.","authors":"Man Luo, Junjie Zhao, Juha Merilä, Rowan D H Barrett, Baocheng Guo, Juntao Hu","doi":"10.1186/s12915-025-02176-0","DOIUrl":"10.1186/s12915-025-02176-0","url":null,"abstract":"<p><strong>Background: </strong>Populations colonizing contrasting environments are likely to undergo adaptive divergence and evolve ecotypes with locally adapted phenotypes. While diverse molecular mechanisms underlying ecotype divergence have been identified, less is known about their interplay and degree of divergence.</p><p><strong>Results: </strong>Here we integrated epigenomic and transcriptomic data to explore the interactions among gene expression, alternative splicing, DNA methylation, and microRNA expression to gauge the extent to which patterns of divergence at the four molecular levels are aligned in a case of postglacial divergence between marine and freshwater ecotypes of nine-spined sticklebacks (Pungitius pungitius). Despite significant genome-wide associations between epigenomic and transcriptomic variation, we found largely non-parallel patterns of ecotype divergence across epigenomic and transcriptomic levels, with predominantly nonoverlapping (ranging from 43.40 to 87.98%) sets of differentially expressed, spliced and methylated genes, and candidate genes targeted by differentially expressed miRNA between the ecotypes. Furthermore, we found significant variation in the extent of ecotype divergence across different molecular mechanisms, with differential methylation and differential splicing showing the highest and lowest extent of divergence between ecotypes, respectively. Finally, we found a significant enrichment of genes associated with ecotype divergence in differential methylation.</p><p><strong>Conclusions: </strong>Our results suggest a nuanced relationship between epigenomic and transcriptomic processes, with alignment at the genome-wide level masking relatively independent effects of different molecular mechanisms on ecotype divergence at the gene level.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"70"},"PeriodicalIF":4.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555950","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":"Switching of OAS1 splicing isoforms overcomes SNP-derived vulnerability to SARS-CoV-2 infection.","authors":"Kei Iida, Masahiko Ajiro, Akiko Nakano-Kobayashi, Yukiko Muramoto, Toru Takenaga, Masatsugu Denawa, Ryo Kurosawa, Takeshi Noda, Masatoshi Hagiwara","doi":"10.1186/s12915-025-02173-3","DOIUrl":"10.1186/s12915-025-02173-3","url":null,"abstract":"<p><strong>Background: </strong>The SARS-CoV-2 pandemic provided important insights into the relationship between infectious diseases and the human genome. A genomic region encoding the 2'-5'-oligoadenylate synthetase (OAS) family proteins that sense viral genomic RNAs and trigger an antiviral response contains single nucleotide polymorphisms (SNPs) associated with SARS-CoV-2 infection susceptibility. A high-risk SNP identified at the splice acceptor site of OAS1 exon 6-a terminal exon-alters the proportion of various splicing isoforms of OAS1 and its activity. However, the actual causality of this SNP or splicing to infection susceptibility remains unknown.</p><p><strong>Results: </strong>In this study, it was found that serine-arginine-rich splicing factor 6 (SRSF6) binds to the splice donor site of the human OAS1 exon 5. SRSF6 determines the selected alternative terminal exon when the risk allele disrupts the splice acceptor site. Subsequently, an inhibitor for CDC-like kinase was rationally selected as a candidate splicing modulator. RNA-Seq and RT-PCR analyses revealed that this inhibitor can induce splice switching of OAS1 mRNAs in the human lung adenocarcinoma cell line Calu-3. Under the inhibitor treatment, the cells exhibited reduced SARS-CoV-2 infection rates. Meanwhile, the colonic epithelial cell line Caco-2 expressed non-risk type OAS1 mRNA isoforms that did not undergo splice-switching or demonstrate altered SARS-CoV-2 sensitivity following treatment with the inhibitor.</p><p><strong>Conclusions: </strong>These results indicate that a high-risk SNP in OAS1 influences cell susceptibility to SARS-CoV-2 infection by inducing splice-switching at its terminal exon. Additionally, chemical splicing modifiers may prove beneficial in overcoming this genomic vulnerability.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"60"},"PeriodicalIF":4.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536568","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":"CTCF-mediated insulation and chromatin environment modulate Car5b escape from X inactivation.","authors":"He Fang, Ana R Tronco, Giancarlo Bonora, Truong Nguyen, Jitendra Thakur, Joel B Berletch, Galina N Filippova, Steven Henikoff, Jay Shendure, William S Noble, Zhijun Duan, Christine M Disteche, Xinxian Deng","doi":"10.1186/s12915-025-02137-7","DOIUrl":"10.1186/s12915-025-02137-7","url":null,"abstract":"<p><strong>Background: </strong>Genes that escape X-chromosome inactivation (XCI) in female somatic cells vary in number and levels of escape among mammalian species and tissues, potentially contributing to species- and tissue-specific sex differences. CTCF, a master chromatin conformation regulator, is enriched at escape regions and may play an important role in regulating escape, but the molecular mechanisms remain elusive.</p><p><strong>Results: </strong>CTCF binding profiles and epigenetic features were systematically examined at escape genes (escapees) using mouse allelic systems with skewed XCI to distinguish the inactive X (Xi) and active X (Xa) chromosomes. We found that six constitutive and two facultative escapees are located inside 30-800 kb domains marked by convergent arrays of CTCF binding sites, consistent with the formation of chromatin loops. Facultative escapees show clear differences in CTCF binding depending on their XCI status in specific cell types/tissues. In addition, sets of strong and in some cases divergent CTCF binding sites located at the boundary between an escapee and its adjacent neighbors subject to XCI would also help insulate domains. Indeed, deletion but not inversion of a CTCF binding site at the boundary between the facultative escapee Car5b and its silent neighbor Siah1b results in a dramatic reduction of Car5b escape. This is associated with reduced CTCF and cohesin binding, which indicates loss of looping and insulation and is supported by 3C combined with Hi-C analysis. In addition, enrichment in the repressive mark H3K27me3 invades the Car5b domain in deleted cells, consistent with loss of expression from the Xi. In contrast, cells with an inversion of the CTCF binding site retain CTCF and cohesin binding, as well as looping, in line with persistence of escape. Interestingly, the levels of escape increase in cells with deletion of either Dxz4, which disrupts the Xi-specific compact 3D structure, or Firre, which results in lower H3K27me3 enrichment on the Xi, indicating that the structural and epigenetic features of the Xi constrain escape from XCI in wild type conditions.</p><p><strong>Conclusions: </strong>Taken together, our findings support the idea that escape from XCI in female somatic cells is modulated by both the topological insulation of domains via CTCF binding and the surrounding heterochromatin environment.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"68"},"PeriodicalIF":4.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536642","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":"Proteomic analysis reveals the alleviation of follicular development defects in offspring mice under DEHP exposure by melatonin.","authors":"Jing-Cai Liu, Yuan-Jing Zou, Kun-Huan Zhang, Yi-Ming Ji, Yue Wang, Shao-Chen Sun","doi":"10.1186/s12915-025-02165-3","DOIUrl":"10.1186/s12915-025-02165-3","url":null,"abstract":"<p><strong>Background: </strong>Environmental endocrine disruptor Di (2-ethylhexyl) phthalate (DEHP) widely affects the health of human and animals including the reproductive system. However, there are few studies on the protective strategies for the maternal DEHP exposure on follicular development of offspring. In the present study, we established a model of lactation female mice exposed to DEHP and reported the effects and potential mechanism of melatonin on the follicular development of offspring.</p><p><strong>Results: </strong>Our data showed that melatonin rescued the decrease of primordial follicles, antral follicles and oocyte number (increased by 74.2%) of offspring caused by maternal DEHP exposure from the primordial follicle formation stage. Proteomic analysis showed that melatonin altered the ovarian steroidogenesis, lipid metabolism, signal transduction, and DNA damage-related proteins. Melatonin reversed the disorder of lipid metabolism caused by DEHP and stabilized ovarian hormone secretase level. Molecular docking results indicated that DEHP/MEHP/melatonin binds to HSD17B2 to form a stable conformation, which may explain the reduction in 17β-estradiol induced by DEHP. Moreover, melatonin restored granulosa cell proliferation, reduced oxidative stress and DNA damage-related apoptosis, enhanced mitochondrial function, and protected ovarian cells. Besides, melatonin enhanced gap junction and promoted intercellular communication, which facilitate the formation of primordial follicles and the growth and development of antral follicles. In addition, melatonin rescued the oocyte defects of offspring caused by maternal DEHP exposure.</p><p><strong>Conclusions: </strong>Taken together, our data showed that melatonin could alleviate the damage of follicular development and abnormal ovarian steroidogenesis of offspring caused by maternal DEHP exposure.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"65"},"PeriodicalIF":4.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531248","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":"ARv7 promotes the escape of prostate cancer cells from androgen deprivation therapy-induced senescence by mediating the SKP2/p27 axis.","authors":"Dian Zhuang, Jinsong Kang, Haoge Luo, Yu Tian, Xiaoping Liu, Chen Shao","doi":"10.1186/s12915-025-02172-4","DOIUrl":"10.1186/s12915-025-02172-4","url":null,"abstract":"<p><strong>Background: </strong>Androgen deprivation therapy (ADT) induces cellular senescence and tumor stasis, thus serving as the standard treatment for prostate cancer (PCa). However, continuous suppression of canonical androgen receptor signaling actually leads to the switch from androgen-responsive growth to androgen-independent growth, contributing to \"escape\" from this ADT-induced senescence (AIS) and, subsequently, the development of castration-resistant prostate cancer (CRPC). Unfortunately, the mechanism underlying this phenomenon remains elusive.</p><p><strong>Results: </strong>In this study, we demonstrated that androgen receptor splicing variant 7 (ARv7), a dominant factor mediating abnormal AR signaling and ADT resistance, is closely associated with outgrowth from AIS of PCa cells. Mechanistically, ARv7 binds to the promoter of SKP2, activating its transcription, and then promotes the proteasomal degradation of the cell cycle regulator p27 and G1/S transition. In addition, we applied bioinformatic and in vitro analyses to show that SKP2 expression level is dramatically inhibited upon ADT, but its reactivation is one key step during the establishment of CRPC. Finally, we also demonstrated that SKP2 inhibitor treatment can significantly inhibit the growth of androgen-independent cell lines and enhance the efficacy of ADT.</p><p><strong>Conclusions: </strong>Our work reveals a novel role of ARv7 in regulating AIS and suggests that targeting the ARv7/SKP2/p27 axis could be a potential strategy to delay disease progression to the CRPC state during prolonged ADT.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"66"},"PeriodicalIF":4.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531224","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":"PPARα regulates YAP protein levels and activity by affecting its ubiquitination modification.","authors":"Wenhong Zhou, Shuaishuai Zhang, Yao Chen, Ziqi Chen, Guofang Bi, Manlan Guo, Xiaowen Jiang, Xiao Yang, Jianhong Fang, Linhu Ye, Shicheng Fan, Huichang Bi","doi":"10.1186/s12915-025-02163-5","DOIUrl":"10.1186/s12915-025-02163-5","url":null,"abstract":"<p><strong>Background: </strong>Peroxisome proliferator-activated receptor α (PPARα) plays a crucial role in liver physiological and pathological processes. Yes-associated protein (YAP) is a key effector in regulating cell growth and organ size. Ubiquitination is known to modulate YAP protein expression, stability, and nuclear localization. Our previous study demonstrated that PPARα activation promotes hepatomegaly and liver regeneration via YAP activation. However, the underlying molecular mechanisms by which PPARα regulates YAP are unclear. In this study, PPARα was activated by the classical agonist WY-14643, and its effects on YAP ubiquitination were examined using plasmid transfection and immunoprecipitation. The ubiquitination of YAP was further investigated through mutant YAP plasmids, gene knockdown, and immunofluorescence staining. YAP mRNA and protein expression were measured via qRT-PCR and western blotting.</p><p><strong>Results: </strong>The results demonstrated that PPARα activation upregulated YAP protein levels and enhanced its activity, while reducing overall YAP ubiquitination. Specifically, PPARα activation inhibited K48-linked ubiquitination while promoting K63-linked ubiquitination of YAP. Mutations at the K252, K321, and K497 residues of YAP markedly reduced the capacity of PPARα activation to facilitate YAP nuclear translocation. Furthermore, knockdown of the E3 ligase TRAF6 abolished the PPARα-induced K63-linked ubiquitination of YAP and the upregulation of its downstream target genes.</p><p><strong>Conclusions: </strong>These findings highlight the pivotal role of ubiquitination in regulating YAP through PPARα activation, providing novel insights for future studies on the post-translational regulation of YAP by PPARα activation.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"64"},"PeriodicalIF":4.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531244","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":"Molecular evolution of dietary shifts in ladybird beetles (Coleoptera: Coccinellidae): from fungivory to carnivory and herbivory.","authors":"Yu-Hao Huang, Hermes E Escalona, Yi-Fei Sun, Pei-Fang Zhang, Xue-Yong Du, Sen-Rui Gong, Xue-Fei Tang, Yuan-Sen Liang, Dan Yang, Pei-Tao Chen, Huan-Ying Yang, Mei-Lan Chen, Bruno Hüttel, Ondrej Hlinka, Xingmin Wang, Karen Meusemann, Adam Ślipiński, Andreas Zwick, Robert M Waterhouse, Bernhard Misof, Oliver Niehuis, Hao-Sen Li, Hong Pang","doi":"10.1186/s12915-025-02174-2","DOIUrl":"10.1186/s12915-025-02174-2","url":null,"abstract":"<p><strong>Background: </strong>Dietary shifts are major evolutionary steps that shape ecological niches and biodiversity. The beetle family Coccinellidae, commonly known as ladybirds, first transitioned from a fungivorous to an insectivorous and subsequently a plant diet. However, the molecular basis of this dietary diversification remained unexplored.</p><p><strong>Results: </strong>We investigated the molecular evolution of dietary shifts in ladybirds, focusing on the transitions from fungivory to carnivory (Coccinellidae) and from carnivory to herbivory (Epilachnini), by comparing 25 genomes and 62 transcriptomes of beetles. Our analysis shows that chemosensory gene families have undergone significant expansions at both nodes of diet change and were differentially expressed in feeding experiments, suggesting that they may be related to foraging. We found expansions of digestive and detoxifying gene families and losses of chitin-related digestive genes in the herbivorous ladybirds, and absence of most plant cell wall-degrading enzymes in the ladybirds dating from the transition to carnivory, likely indicating the effect of different digestion requirements on the gene repertoire. Immunity effector genes tend to emerge or have specific amino acid sequence compositions in carnivorous ladybirds and are downregulated under suboptimal dietary treatments, suggesting a potential function of these genes related to microbial symbionts in the sternorrhynchan prey.</p><p><strong>Conclusions: </strong>Our study provides a comprehensive comparative genomic analysis to address evolution of chemosensory, digestive, detoxifying, and immune genes associated with dietary shifts in ladybirds. Ladybirds can be considered a ubiquitous example of dietary shifts in insects, and thus a promising model system for evolutionary and applied biology.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"67"},"PeriodicalIF":4.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531227","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":"Transcriptomic profile of RNA pseudouridine modification as a biomarker for cellular senescence associated with survival outcomes in colorectal cancer.","authors":"Yingguo Gan, Ze Yuan, Jingrong Weng, Mingzhe Huang, Tuoyang Li, Yuanhui Wu, Kaixin Lin, Junyi Han, Xuan Li, Haotian Liu, Zixiao Wan, Ziming Li, Zhenghua Chen, Ji Cui, Yanxin Luo, Meijin Huang, Huichuan Yu, Jinxin Lin","doi":"10.1186/s12915-025-02170-6","DOIUrl":"10.1186/s12915-025-02170-6","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is considered as an age-related disease, and cellular senescence (CS) plays a crucial role in cancer development and progression. Previous studies have shown the role of epigenetic changes in aging and cancer development, but the role of RNA pseudouridine (Ψ) modification in aging and cancer remains to be explored.</p><p><strong>Results: </strong>Using bulk RNA sequencing, CRC cells with low Ψ writers expression levels have higher CS levels. We developed the Psi Score for assessing the transcriptomic profile of RNA Ψ modification regulation and found that the Psi Score correlates with CS. Furthermore, Psi-related senescence may be mediated by mTOR, TGF-β, TNF-α, and inflammatory response signaling pathways. Meanwhile, Psi Score could predict the anti-cancer treatment outcomes of anti-aging interventions and could be used to predict the response to immunotherapy.</p><p><strong>Conclusions: </strong>Overall, these findings reveal that RNA Ψ modification connected aging and cancer and provided novel insights into biomarker-guided cancer regimens.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"61"},"PeriodicalIF":4.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522729","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}