FEBS Letters最新文献

{"title":"The power of microRNA regulation—insights into immunity and metabolism","authors":"Stefania Oliveto,&nbsp;Nicola Manfrini,&nbsp;Stefano Biffo","doi":"10.1002/1873-3468.70039","DOIUrl":"10.1002/1873-3468.70039","url":null,"abstract":"<p>MicroRNAs (miRNAs) are a prominent class of small non-coding RNAs that control gene expression. This comprehensive review explores the intricate roles of miRNAs in metabolism and immunity, as well as the emerging field of immunometabolism. The core of this work delves into the functional and regulatory capabilities of miRNAs, examining their complex influence on glucose and lipid metabolism, as well as their pivotal roles in shaping T-cell development and function. Specifically, this review addresses how miRNAs orchestrate the complex interaction between cellular metabolic processes and immune responses, underscoring the essential nature of these small regulatory molecules in maintaining homeostasis. Finally, we examine the emerging role of Artificial Intelligence (AI) in miRNA research, focusing on how machine learning techniques are revolutionizing the identification and validation of potential miRNA biomarkers. By integrating these diverse aspects, this review underscores the multifaceted roles of miRNAs in biological processes and their significant potential in advancing biomedical research and clinical applications.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 13","pages":"1821-1851"},"PeriodicalIF":3.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C-terminal anchor endolysins—proposing a third class of tailed bacteriophage endolysins","authors":"Elina Cernooka,&nbsp;Nikita Zrelovs,&nbsp;Andris Kazaks","doi":"10.1002/1873-3468.70042","DOIUrl":"10.1002/1873-3468.70042","url":null,"abstract":"<p>Endolysins—enzymes produced by tailed bacteriophages to degrade bacterial cell walls—have traditionally been classified as canonical or signal-anchor-release (SAR) endolysins. However, analysis of expanding viral (meta)genomic data has revealed a third class, which we designate as C-terminal anchor (CTA) endolysins. These enzymes feature an N-terminal enzymatic domain, a C-terminal transmembrane domain, and typically lack signal sequences, distinguishing them from SAR endolysins. CTA endolysins span all known enzymatic activities and exhibit diverse architectures, though most have a single transmembrane helix and an N-out, C-in topology, consistent with periplasmic activity. While their functional mechanisms remain to be elucidated, our findings suggest that CTA endolysins are nearly as prevalent as SAR endolysins and represent a distinct, previously unrecognized branch of the endolysin world.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 11","pages":"1499-1508"},"PeriodicalIF":3.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981363","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}

{"title":"Identification of novel small molecule inhibitors of ETS transcription factors","authors":"Shaima Abdalla,&nbsp;Zary Forghany,&nbsp;Jin Ma,&nbsp;Johan G. Hollander,&nbsp;Ruta Nachane,&nbsp;Karoly Szuhai,&nbsp;Pancras C. W. Hogendoorn,&nbsp;Peter ten Dijke,&nbsp;Dipen Shah,&nbsp;David A. Baker","doi":"10.1002/1873-3468.70040","DOIUrl":"10.1002/1873-3468.70040","url":null,"abstract":"<p>The evolutionarily conserved E-Twenty-Six (ETS) family of transcription factors acts downstream of major signal transduction pathways and plays a pivotal role in tissue development and maintenance. Importantly, their function is frequently corrupted in a substantial proportion of tumour types, and they are also indispensable for angiogenic sprouting, a hallmark of cancer, which is essential for fuelling tumour enlargement and dissemination. Consequently, targeting aberrant ETS activity could potentially represent a precise and effective means by which to block tumour growth. Here, we present proof-of-principle high-throughput screens and an initial characterization of candidate hits, as a methodological and conceptual framework for the identification of novel ETS transcription factor inhibitors, which may ultimately lead to new therapeutic avenues for treating cancer.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 12","pages":"1733-1748"},"PeriodicalIF":3.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Septin2 regulates ARHGAP25-mediated suppression of lamellipodia formation and cell spreading","authors":"Tomoe Tamura,&nbsp;Emi Umekawa,&nbsp;Mamiko Mori,&nbsp;Mayuko Otsuki,&nbsp;Yoshio Shibagaki,&nbsp;Seisuke Hattori,&nbsp;Takeyuki Sugawara,&nbsp;Koji Saito,&nbsp;Yasutaka Ohta","doi":"10.1002/1873-3468.70041","DOIUrl":"10.1002/1873-3468.70041","url":null,"abstract":"<p>Rho family small GTPases are key regulators of the actin cytoskeletal organization that controls cell morphology, but the regulatory mechanism of Rho small GTPase activity is not fully understood. Here we identified septin2, a component of the septin cytoskeleton, as an interacting protein of ARHGAP25, a GTPase-activating protein for Rho small GTPase Rac, in mammalian cells. ARHGAP25 colocalized with septin2 at lamellipodia, which are actin filament-rich protrusions. Overexpression of ARHGAP25 suppressed Rac-dependent lamellipodia formation and cell spreading, and ARHGAP25-mediated suppression was restored by depletion of septin2. Forced expression of septin2 enhanced ARHGAP25-mediated suppression of cell spreading, and septin2-enhanced suppression was restored by the depletion of ARHGAP25. These results suggest that septin2 controls cell morphology by regulating the function of ARHGAP25.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 11","pages":"1582-1594"},"PeriodicalIF":3.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958309","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}

{"title":"Fanzors, a family of eukaryotic RNA-guided DNA endonucleases","authors":"Kaiyi Jiang,&nbsp;Jonathan S. Gootenberg,&nbsp;Omar O. Abudayyeh","doi":"10.1002/1873-3468.70038","DOIUrl":"10.1002/1873-3468.70038","url":null,"abstract":"<p>Fanzor proteins represent the first confirmed family of RNA-guided DNA endonucleases in eukaryotes. Originally identified in 2013 as TnpB homologs, Fanzors remained functionally uncharacterized until 2023, when three independent research groups demonstrated their activity as programmable nucleases. Comprehensive bioinformatic analysis revealed over 3000 unique Fanzor sequences across diverse eukaryotic phyla and viruses. Fanzors share core mechanisms with their prokaryotic counterparts, utilizing a RuvC domain for DNA cleavage and requiring a Fanzor RNA (ωRNA) for targeting. However, they exhibit distinctive features, including diverse target adjacent motif preferences, extended ωRNA structure, and RuvC domain rearrangements. The eukaryotic origins of Fanzors make them promising tools for mammalian genome editing, with initial studies demonstrating successful editing in human cells without extensive engineering.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 8","pages":"1089-1093"},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cells of all trades - on the importance of spatial positioning of senescent cells in development, healing and aging.","authors":"Helene Dworak, Tomaz Rozmaric, Johannes Grillari, Mikolaj Ogrodnik","doi":"10.1002/1873-3468.70037","DOIUrl":"10.1002/1873-3468.70037","url":null,"abstract":"<p><p>Biological processes are often spatially regulated, ensuring molecular and cellular events occur in their most strategically advantageous locations. Cellular senescence, marked by cell cycle arrest and hypersecretion, is recognized as an important part of physiological processes like development and healing, but it also contributes to aging and disease. However, the spatial distribution of senescent cells and its physiological and pathological impact remain unclear. Here we compile evidence on senescent cell localization in development, healing, and aging. We emphasize the significance of their spatial patterns and speculate on the effects of disrupted spatial positioning of senescence in relation to pathologies. To summarize the specific spatial functions of senescent cells, we propose to refer to them as 'barrier' and 'conductor' functions. The 'barrier' function of senescent cells, due to their altered morphology and apoptosis resistance, separates tissues and builds a border between two environments. The conductor function, with the secretion of signaling factors, influences the surrounding area and stimulates migration, differentiation, or proliferation, among other processes. Overall, this Review explores the spatial patterning of cellular senescence in biological processes, highlighting its dual roles as 'barrier' and 'conductor' functions, and examines the implications of senescent cell distribution in development, healing, aging, and disease.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining the NaV1.7 pharmacophore of a class of venom-derived peptide inhibitors via a combination of in silico screening and rational engineering","authors":"Gagan Sharma,&nbsp;Jennifer R. Deuis,&nbsp;Xinying Jia,&nbsp;Theo Crawford,&nbsp;Sassan Rahnama,&nbsp;Eivind A. B. Undheim,&nbsp;Irina Vetter,&nbsp;Yanni K. -Y. Chin,&nbsp;Mehdi Mobli","doi":"10.1002/1873-3468.70036","DOIUrl":"10.1002/1873-3468.70036","url":null,"abstract":"<p>Ion channels are among the main targets of venom peptides. Extensive functional screening has identified a number of these peptides as modulators of the voltage-gated sodium channel subtype Na_V1.7, a potential target for the treatment of chronic pain. In this study, we used a bioinformatic approach that can automatically identify Na_V1.7 gating modifier toxins from sequence information alone. The method further enables the incorporation of evolutionarily accessible sequence space in structure–activity relationship studies. The <i>in silico</i> method identified a putative Na_V1.7 inhibitor, μ-theraphotoxin Cg4a, which we produced recombinantly and confirmed as a Na_V1.7 inhibitor. Using structural and mutagenesis studies, we propose an improved definition of the pharmacophore of this class of Na_V1.7 inhibitors, aiding future <i>in silico</i> screening and classification of Na_V1.7 inhibitors.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 12","pages":"1717-1732"},"PeriodicalIF":3.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization and multifunctionality of two amino acid aminotransferases from the hyperthermophile Thermotoga maritima","authors":"Tetsuya Miyamoto,&nbsp;Yurina Iguchi,&nbsp;Ayasa Tada,&nbsp;Mauka Arai,&nbsp;Kumiko Sakai-Kato","doi":"10.1002/1873-3468.70034","DOIUrl":"10.1002/1873-3468.70034","url":null,"abstract":"<p>The hyperthermophile <i>Thermotoga maritima</i> possesses a unique peptidoglycan containing an unusual <span>d</span>-lysine. Previously, we identified enzymes involved in the production of <span>d</span>-lysine and <span>d</span>-glutamate, respectively, but the biosynthetic pathway of <span>d</span>-alanine remains unclear. Herein, we characterized two amino acid aminotransferases, aspartate aminotransferase (TM1255), and alanine aminotransferase (TM1698). TM1255 has specific aminotransferase activities toward <span>l</span>-aspartate and <span>l</span>-glutamate as amino donors, while TM1698 has broad substrate specificity with high activities toward <span>l</span>-alanine and <span>l</span>-aminobutyrate as amino donors. Intriguingly, these two enzymes possess racemase activities toward several amino acids and aspartate 4-decarboxylase activity. The catalytic efficiency of both enzymes was highest for aminotransferase activity, followed by aspartate 4-decarboxylase activity. Therefore, TM1255 and TM1698 are novel multifunctional enzymes that have three different activities.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 8","pages":"1187-1200"},"PeriodicalIF":3.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729388","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}

{"title":"EXPRESSION OF CONCERN: Pre-Symptomatic Detection of Prions by Cyclic Amplification of Protein Misfolding","authors":"","doi":"10.1002/1873-3468.70035","DOIUrl":"10.1002/1873-3468.70035","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN:</b> C. Soto, L. Anderes, S. Suardi, F. Cardone, J. Castilla, M.-J. Frossard, S. Peano, P. Saa, L. Limido, M. Carbonatto, J. Ironside, J.-M. Torres, M. Pocchiari, and F. Tagliavini, “Pre-Symptomatic Detection of Prions by Cyclic Amplification of Protein Misfolding,” <i>FEBS Letters</i> 579, no. 3 (2005): 638-642, https://doi.org/10.1016/j.febslet.2004.12.035.</p><p>This Expression of Concern is for the above article, published online on 25 December 2004, in Wiley Online Library (http://onlinelibrary.wiley.com/) and has been issued by agreement between the journal Editor-in-Chief, Michael Brunner; FEBS Press; and John Wiley and Sons Ltd. The journal received a report from a third party that there was evidence of undeclared spliced sections in Figure 2 and Figure 4 as well as a duplication of bands between those two figures. An investigation by the journal confirmed these concerns and detected additional evidence of undeclared splicing in Figure 3. The investigation also uncovered evidence of manipulation on non-data-containing portions of the western blot images in Figure 1. The authors responded to an inquiry by the publisher and have stated that they are not able to supply the original data due to the length of time since publication. In their response, the authors proposed a correction to change the duplicated lanes in Figure 4 to lanes from alternate experiments performed at the time, for which the authors have the original data. However, the parties concluded that this correction would not be appropriate. The authors also stated that non-data-containing elements of the western blots in Figure 1 may have been altered to improve readability, but the journal is not able to confirm this in the absence of raw data. The parties are concerned about the issues identified but also believe that they do not necessarily invalidate the conclusions of the paper. The parties agree with an Expression of Concern because the veracity of the experimental data could not be confirmed by viewing the original raw data. Authors C. Soto, J. Castilla, and F. Tagliavini agree with the Expression of Concern. All other authors could not be reached regarding the Expression of Concern.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 7","pages":"1086"},"PeriodicalIF":3.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clioquinol induces mitochondrial toxicity in SH-SY5Y neuroblastoma cells by affecting the respiratory chain complex IV and OPA1 dynamin-like GTPase","authors":"Masato Katsuyama,&nbsp;Noriaki Arakawa,&nbsp;Takeshi Yaoi,&nbsp;En Kimura,&nbsp;Misaki Matsumoto,&nbsp;Kazumi Iwata,&nbsp;Atsushi Umemura,&nbsp;Chihiro Yabe-Nishimura","doi":"10.1002/1873-3468.70033","DOIUrl":"10.1002/1873-3468.70033","url":null,"abstract":"<p>Clioquinol has been thought of as the causative drug of subacute myelo-optic neuropathy (SMON). The underlying mechanisms of clioquinol toxicity, however, have not been elucidated in detail. Here, we revealed that clioquinol (20 μ<span>m</span>) suppressed the expression of SCO1 and SCO2 copper chaperones for mitochondrial respiratory chain Complex IV (cytochrome c oxidase) in SH-SY5Y neuroblastoma cells. The assembly of Complex IV components and Complex IV activity were suppressed in clioquinol-treated cells. Clioquinol (10–50 μ<span>m</span>) decreased cellular ATP levels in glucose-free media. Clioquinol (10–50 μ<span>m</span>) induced OMA1 mitochondrial protease-dependent degradation of the dynamin-related GTPase OPA1 and suppressed the expression of CHCHD10 and CHCHD2 involved in the maintenance of cristae structure. These results suggest that mitochondrial toxicity is one of the mechanisms of clioquinol-induced neuronal cell death.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 8","pages":"1135-1145"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691600","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}