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Comprehensive analysis of mRNA 3' ends during early zebrafish development reveals dynamics of 3'UTR changes on a genome-wide scale. 对早期斑马鱼发育过程中mRNA 3‘末端的综合分析揭示了全基因组范围内3’ utr变化的动态。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-07-01 DOI: 10.1002/1873-3468.70106
Ludivine Fierro, Anna Ishii, Haruka Aoyama, Toshihiro Arae, Yukako Chiba, Tomoya Kotani
{"title":"Comprehensive analysis of mRNA 3' ends during early zebrafish development reveals dynamics of 3'UTR changes on a genome-wide scale.","authors":"Ludivine Fierro, Anna Ishii, Haruka Aoyama, Toshihiro Arae, Yukako Chiba, Tomoya Kotani","doi":"10.1002/1873-3468.70106","DOIUrl":"https://doi.org/10.1002/1873-3468.70106","url":null,"abstract":"<p><p>Eggs accumulate more than 10 000 mRNAs, from which proteins are synthesized constitutively or in a temporally controlled manner. Although changes in the translation state of these mRNAs are crucial for early development, how embryos orchestrate them remains unclear. Here, we investigated changes in mRNA 3' untranslated regions (UTRs) using 3' end-RNA sequencing of zebrafish embryos and computational methods. Consistent with our previous finding that pou5f3 mRNA is shortened at the 3'UTR during early development, thousands of mRNAs showed shortening of the 3'UTRs. Moreover, we found that most mRNAs in embryos contained several different 3' ends and their proportion was dynamically changed. These changes were coupled with protein synthesis. Our results reveal genome-wide 3'-end dynamics in the regulation of biological processes.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell insights into the role of T cells in B-cell malignancies. 单细胞观察T细胞在b细胞恶性肿瘤中的作用。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-06-26 DOI: 10.1002/1873-3468.70099
Laura Llaó-Cid
{"title":"Single-cell insights into the role of T cells in B-cell malignancies.","authors":"Laura Llaó-Cid","doi":"10.1002/1873-3468.70099","DOIUrl":"https://doi.org/10.1002/1873-3468.70099","url":null,"abstract":"<p><p>The intricate interplay between T cells and tumor cells in B-cell malignancies has garnered significant attention in recent years. Single-cell technologies have revolutionized our understanding of this dynamic relationship, offering unprecedented resolution and insights into cellular heterogeneity, signaling pathways, and immune interactions. This review synthesizes the recent findings that single-cell methodologies have elucidated on the roles of T cells in the pathogenesis, progression, and therapeutic response of B-cell malignancies. Key discoveries include the identification of previously unknown T-cell subsets and their functional states, as well as the mechanisms of immune evasion by malignant B cells. These insights pave the way for innovative therapeutic strategies aimed at harnessing the immune system to combat B-cell lymphomas.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The microtubule-binding domain of spastin participates in microtubule severing through electrostatic interactions. spastin的微管结合域通过静电相互作用参与微管切断。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-06-26 DOI: 10.1002/1873-3468.70105
Pengpeng Yu, Ziyang Wang, Maorong Wen, Wei Chen, Xin Liang, Chunguang Wang
{"title":"The microtubule-binding domain of spastin participates in microtubule severing through electrostatic interactions.","authors":"Pengpeng Yu, Ziyang Wang, Maorong Wen, Wei Chen, Xin Liang, Chunguang Wang","doi":"10.1002/1873-3468.70105","DOIUrl":"https://doi.org/10.1002/1873-3468.70105","url":null,"abstract":"<p><p>Spastin is a microtubule-severing enzyme and takes part in various microtubule-based events, but its microtubule-severing mechanism remains largely elusive. Spastin has an intrinsically unstructured microtubule-binding domain (MTBD) N-terminal to the AAA domain that is indispensable for the microtubule-severing activity. By performing a series of mutagenesis studies, we find that spastin can tolerate the mutation of a small number of basic residues in the MTBD, but mutating half of the basic residues abolishes the basal and microtubule-stimulated ATPase activities of spastin. The isolated MTBD pellets an equal molar amount of tubulin into curl and ring assemblies. Moreover, spastin with a sequence-reversed MTBD is active in ATP hydrolysis and microtubule severing. These results suggest that the MTBD of spastin participates in microtubule severing by making electrostatic interactions with microtubule protofilaments.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cystic fibrosis as a paradigmatic disease in bringing science to the bedside. 囊性纤维化是将科学带到床边的典型疾病。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-06-26 DOI: 10.1002/1873-3468.70101
Margarida D Amaral, Ines Pankonien
{"title":"Cystic fibrosis as a paradigmatic disease in bringing science to the bedside.","authors":"Margarida D Amaral, Ines Pankonien","doi":"10.1002/1873-3468.70101","DOIUrl":"https://doi.org/10.1002/1873-3468.70101","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is a recessive disorder caused by mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR), a chloride/bicarbonate channel that balances fluid homeostasis in epithelia. CFTR dysfunction results in chronic lung infections, pancreatic insufficiency, and salty sweat. Since the discovery of the CFTR gene in 1989, a unique scientific community in both academia and industry has significantly increased our understanding of CF mechanisms. Such knowledge led to spectacular advancements in treatment, from symptom management to CFTR modulators (CFTRm) that alter the mutant protein properties in a mutation-specific way, significantly improving life quality and expectancy of people with CF (pwCF). Emerging genotype-agnostic approaches, such as gene/mRNA therapy, hold promise for future curative treatments for all pwCF. In parallel, precision medicine is revolutionizing CF care through patient-specific therapies, namely for pwCF with genotypes not eligible for CFTRm. However, challenges remain, including high treatment costs, accessibility issues, variable patient responses, and, importantly, the high cancer propensity in pwCF. CF is a model for translational medicine, highlighting the relevance of fundamental research. Insights gained from CF research may also inform therapeutic advancements for other (genetic) diseases.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Insights into pegRNA design from editing of the cardiomyopathy-associated phospholamban R14del mutation. 编辑心肌病相关磷蛋白R14del突变对pegRNA设计的见解
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-06-24 DOI: 10.1002/1873-3468.70097
Bing Yao, Qiangbing Yang, Christian J B Snijders Blok, Mark A Daniels, Pieter A Doevendans, Raymond Schiffelers, Joost P G Sluijter, Zhiyong Lei
{"title":"Insights into pegRNA design from editing of the cardiomyopathy-associated phospholamban R14del mutation.","authors":"Bing Yao, Qiangbing Yang, Christian J B Snijders Blok, Mark A Daniels, Pieter A Doevendans, Raymond Schiffelers, Joost P G Sluijter, Zhiyong Lei","doi":"10.1002/1873-3468.70097","DOIUrl":"https://doi.org/10.1002/1873-3468.70097","url":null,"abstract":"<p><p>Prime editing (PE) represents a transformative genome-editing technology and enables precise insertions, deletions, and base substitutions without introducing double-strand breaks, thereby reducing undesired indels and off-target effects. Despite advancements in enhanced prime editors and optimized prime editing guide RNAs (pegRNAs), designing effective pegRNAs remains a major challenge. The phospholamban (PLN) R14del mutation is associated with cardiomyopathies, making it a crucial target for precise gene-editing strategies. In this study, we explored pegRNA features that contribute to high editing efficiency using the FluoPEER.PLN R14del reporter cell line. Through systematic screening, we identified three pegRNAs with significantly enhanced editing efficiency. Our findings underscore the importance of pegRNA secondary structure and stability in optimizing prime editing, providing valuable insights into precise gene correction strategies.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A rapid in vivo assay to study the regulation of gene expression. 研究基因表达调控的快速体内实验。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-06-17 DOI: 10.1002/1873-3468.70096
Saubhik Som, Gopalapura J Vishalakshi, Lekha E Manjunath, Debraj Manna, Kirtana Vasu, Anumeha Singh, Humaira Siddiqua, Sandeep M Eswarappa
{"title":"A rapid in vivo assay to study the regulation of gene expression.","authors":"Saubhik Som, Gopalapura J Vishalakshi, Lekha E Manjunath, Debraj Manna, Kirtana Vasu, Anumeha Singh, Humaira Siddiqua, Sandeep M Eswarappa","doi":"10.1002/1873-3468.70096","DOIUrl":"https://doi.org/10.1002/1873-3468.70096","url":null,"abstract":"<p><p>Traditional in vivo studies of gene regulation often require labor-intensive protocols and animal sacrifice. Here, we present a minimally invasive method-In Vivo Imaging of Subcutaneous Luminescence (IVISc-L)-for analyzing gene regulation in live mice. The assay involves subcutaneous injection of plasmid DNA encoding firefly luciferase, the expression of which is controlled by the regulatory mechanism under investigation. Luminescence from the injection site is detected and quantified noninvasively using an in vivo imaging system within 24 h. We demonstrate the utility of this approach to study promoter activity, microRNA-mediated regulation, stop codon readthrough, and rare codon effects. IVISc-L eliminates the need for tissue extraction, offering a rapid and scalable platform for investigating gene expression dynamics and screening gene regulatory modulators in vivo.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An amphipol-stabilized multi-pass transmembrane protein as an immunogen to generate mouse memory B cells against native VMAT2. 一种双极性稳定的多代跨膜蛋白作为免疫原产生小鼠记忆B细胞对抗天然VMAT2。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-06-17 DOI: 10.1002/1873-3468.70092
Jiping Yang, Tao Liu, Xianqing Mai, Shengyan Kong, Jingjing He, Zhenhua Wang, Jie Shen, Xiaohua He, Yongmei Xing, Hongwu Qian, Pei Tong
{"title":"An amphipol-stabilized multi-pass transmembrane protein as an immunogen to generate mouse memory B cells against native VMAT2.","authors":"Jiping Yang, Tao Liu, Xianqing Mai, Shengyan Kong, Jingjing He, Zhenhua Wang, Jie Shen, Xiaohua He, Yongmei Xing, Hongwu Qian, Pei Tong","doi":"10.1002/1873-3468.70092","DOIUrl":"https://doi.org/10.1002/1873-3468.70092","url":null,"abstract":"<p><p>Multi-pass transmembrane proteins (MPTPs) are essential for sensing and processing cellular signals and are the primary drug targets of more than half of the approved drugs, the majority being small molecules. However, monoclonal antibodies with favorable properties in modulating MPTPs are rare. Such antibody discovery is limited by the challenging preparation of correctly folded antigens and the generation of antibodies against the natural conformation of MPTPs. Here, we developed an amphipol-trapped antigen as an immunogen and induced efficient mouse memory B cell responses. We generated antibodies unbiasedly by culturing single memory B cells and characterized their specificities. We implemented our strategy to generate high-affinity antibodies against the native conformation of vesicular monoamine transporter 2 (VMAT2; also known as SLC18A2), demonstrating the potential use in discovering antibodies against MPTPs for therapeutics.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Purification tags markedly affect self-aggregation of CPEB3. 纯化标签显著影响CPEB3的自聚集。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-06-17 DOI: 10.1002/1873-3468.70090
Harunobu Saito, Yujin Lee, Motoharu Ueno, Naotaka Sekiyama, Masatomo So, Ayako Furukawa, Kenji Sugase
{"title":"Purification tags markedly affect self-aggregation of CPEB3.","authors":"Harunobu Saito, Yujin Lee, Motoharu Ueno, Naotaka Sekiyama, Masatomo So, Ayako Furukawa, Kenji Sugase","doi":"10.1002/1873-3468.70090","DOIUrl":"https://doi.org/10.1002/1873-3468.70090","url":null,"abstract":"<p><p>Since protein aggregation-including liquid-liquid phase separation (LLPS) and amyloid fibril formation-plays a critical role in both diseases and biological functions, understanding the mechanisms underlying protein aggregation is essential. Recombinant proteins are commonly used in vitro to investigate protein aggregation processes. However, if the purification tags remain uncleaved, they may affect the results and hinder accurate interpretation. Our findings demonstrate that the His<sub>6</sub>-GFP and His<sub>12</sub> tags significantly affect liquid droplet and amyloid fibril formation in the intrinsically disordered region (IDR) of mouse cytoplasmic polyadenylation element-binding protein 3 (CPEB3) and its fragments. This study shows that the purification tags significantly affect aggregation assays, making it essential to account for their influence to accurately interpret protein aggregation.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Crystal structures reveal how the multispecific antibody G2 achieves binding to different peptides 晶体结构揭示了多特异性抗体G2如何与不同肽结合。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-06-17 DOI: 10.1002/1873-3468.70095
Yuya Hanazono, Saaya Yabuno, Takahiro Hayashi, Nobutaka Numoto, Yuji O. Kamatari, Nobutoshi Ito, Masayuki Oda
{"title":"Crystal structures reveal how the multispecific antibody G2 achieves binding to different peptides","authors":"Yuya Hanazono,&nbsp;Saaya Yabuno,&nbsp;Takahiro Hayashi,&nbsp;Nobutaka Numoto,&nbsp;Yuji O. Kamatari,&nbsp;Nobutoshi Ito,&nbsp;Masayuki Oda","doi":"10.1002/1873-3468.70095","DOIUrl":"10.1002/1873-3468.70095","url":null,"abstract":"<p>Monoclonal antibody G2, obtained via immunization with the chicken prion protein (ChPrP), has unique antigen-binding specificity. G2 specifically binds to the ChPrP-derived peptide (Pep18mer) as expected, but also to three other peptides. In this study, we determined the crystal structures of G2 single-chain Fv antibodies covalently linked to Pep18mer and another peptide, PepH4P6. Both bound peptides formed similar U-shaped structures that stuck into the G2 antigen-binding pocket. Their three-dimensional structures were stabilized by interactions within the peptides, and the structure of the bound Pep18mer was similar to that of the corresponding ChPrP region. G2 acquired the binding ability to both Pep18mer and PepH4P6 via deletion of the 95th residue of the light chain during affinity maturation, consistent with our structural analysis.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 13","pages":"1925-1934"},"PeriodicalIF":3.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chelatase activity of magnesium dechelatase associated with chlorophyll degradation. 与叶绿素降解相关的镁脱羧酶的螯合酶活性。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-06-17 DOI: 10.1002/1873-3468.70094
Soma Sato, Mitsuaki Hirose, Hitoshi Tamiaki, Hisashi Ito
{"title":"Chelatase activity of magnesium dechelatase associated with chlorophyll degradation.","authors":"Soma Sato, Mitsuaki Hirose, Hitoshi Tamiaki, Hisashi Ito","doi":"10.1002/1873-3468.70094","DOIUrl":"https://doi.org/10.1002/1873-3468.70094","url":null,"abstract":"<p><p>Metalated tetrapyrrole molecules play crucial roles in respiration, photosynthesis, and biocatalysis. In this study, the chelatase activity of the bacterial magnesium dechelatase homologous gene, which encodes an enzyme that extracts the central magnesium ion from chlorophyll, was demonstrated. The recombinant protein inserted metal ions, such as zinc, into methyl pyropheophorbide a, a synthetic derivative of chlorophyll a. Mutation analysis and structural modeling suggested H32, D34, and D62 as key residues involved in coordinating metal ions and facilitating proton extraction from methyl pyropheophorbide a. Chelatase activity was also found in the recombinant plant magnesium dechelatase protein. The bacterial gene complemented Escherichia coli ferrochelatase mutants. These findings provide novel insights into the mechanisms underlying chelation reactions.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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