FEBS LettersPub Date : 2025-07-09DOI: 10.1002/1873-3468.70107
Katri Vainionpää, Ahmed B. Montaser, Henri Leinonen
{"title":"Cyclic nucleotide signaling as a drug target in retinitis pigmentosa","authors":"Katri Vainionpää, Ahmed B. Montaser, Henri Leinonen","doi":"10.1002/1873-3468.70107","DOIUrl":"10.1002/1873-3468.70107","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerative diseases caused by mutations in over 90 genes. The complexity of its genetic background and economic barriers limit the broad application of targeted gene therapies. Therefore, general pharmacological strategies to slow disease progression, regardless of the underlying mutation, are needed. Cyclic nucleotide second messengers, such as cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), are important for normal retinal function. This includes phototransduction, for which cGMP signaling is essential. Dysregulation of the cyclic nucleotide systems is associated with retinal degeneration, and the inhibition of cGMP or cAMP signaling has shown beneficial effects in several retinal degeneration disease models. Here, we propose these systems as drug targets for RP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <div>\u0000 \u0000 <div>\u0000 \u0000 <h3>Impact statement</h3>\u0000 <p>This perspective proposes targeting cyclic nucleotide signaling (cGMP and cAMP) as a mutation-independent therapeutic strategy for retinitis pigmentosa, offering broad potential for disease-modifying treatment potentially through drug repurposing and novel drug delivery systems.</p>\u0000 </div>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 18","pages":"2557-2570"},"PeriodicalIF":3.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590770","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}
FEBS LettersPub Date : 2025-07-09DOI: 10.1002/1873-3468.70112
Carl Peter J Maury
{"title":"Origin of life: β-sheet amyloid conformers as the primordial functional polymers on the early Earth and their role in the emergence of complex dynamic networks.","authors":"Carl Peter J Maury","doi":"10.1002/1873-3468.70112","DOIUrl":"https://doi.org/10.1002/1873-3468.70112","url":null,"abstract":"<p><p>The origin of life has remained a conundrum. Among the origin-of-life hypotheses, the RNA world has gained wide popularity. It has, however, been difficult to explain the emergence of both stable and meaningful RNA under the presumably very harsh early Earth conditions, and it has been assumed that some other replicating system must have preceded the RNA world. The amyloid world hypothesis posits that the first functional polymers on the primitive Earth were structurally stable self-replicating β-sheet-based peptide amyloids. The amyloid hypothesis is examined in this perspective in light of new research results and highlights the role of dynamic interacting networks. The mechanisms of self-amplification and information transfer are discussed, as well as the catalytic, adaptive, and evolutionary properties of the cross-β-sheet ensembles. There is no contradiction between the amyloid and the RNA world hypotheses: In the harsh prebiotic environment, the β-sheet fibrillar networks provide a scaffold and initial protection for nucleobases and other prebiotic compounds, and the cooperative interactions of the β-sheet ensembles with nucleic acids, fatty acids, and natively folded proteins are in concert with the view of an early co-evolving amyloid-RNA-lipid-protein world.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599783","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}
FEBS LettersPub Date : 2025-07-07DOI: 10.1002/1873-3468.70111
Ippei Koshi, Shigeaki Hida, Ryuuichi Nishinakamura, Hideki Sanjo, Shinsuke Taki
{"title":"ShcA activation via Tyr573 of the IL-3/IL-5/GM-CSF receptor βc signals for IL-4 production in mouse primary basophils","authors":"Ippei Koshi, Shigeaki Hida, Ryuuichi Nishinakamura, Hideki Sanjo, Shinsuke Taki","doi":"10.1002/1873-3468.70111","DOIUrl":"10.1002/1873-3468.70111","url":null,"abstract":"<p>Granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 signals are transmitted via the shared receptor subunit common β (βc). Earlier studies showed that distinct subdomains and tyrosine residues of βc are connected to specific downstream signaling pathways. However, as most of those pathways are for survival/proliferation, much remains to be learned about how βc transmits signals for effector functions. Here, by reconstituting primary βc-deficient basophils with βc mutants, we found that the tyrosine 573 of βc was required for recruiting and phosphorylating the adaptor ShcA and IL-4 production. Furthermore, dominant-negative ShcA and the ShcA inhibitor idebenone inhibited IL-4 production but not cell survival. These results provided further insight into how the functional pleiotropy of cytokines is supported by the structure of their receptors.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 18","pages":"2663-2673"},"PeriodicalIF":3.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947664","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}
FEBS LettersPub Date : 2025-07-04DOI: 10.1002/1873-3468.70102
Daniel Bachurski, Michael Hallek
{"title":"Biological and technical complexities in analyzing extracellular vesicle immune interactions in B-cell malignancies.","authors":"Daniel Bachurski, Michael Hallek","doi":"10.1002/1873-3468.70102","DOIUrl":"10.1002/1873-3468.70102","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) mediate intercellular communication in tumor immune microenvironments. However, their role in B-cell malignancies remains poorly defined, owing to biological complexity and technical challenges in EV isolation and analysis. Advancing EV and recipient cell analysis at the single-EV and single-cell level via novel tagging strategies is essential to overcome these obstacles. This graphical review examines the heterogeneity of EV cargo and subpopulation composition from diverse sources and their immune interactions in the tumor immune microenvironment of B-cell malignancies, while discussing innovative methods for analyzing immune cell EVs and their target cells.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559559","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}
FEBS LettersPub Date : 2025-07-04DOI: 10.1002/1873-3468.70098
Igor Zivkovic, Morana Dulic, Ita Gruic-Sovulj
{"title":"Mechanisms and kinetic assays of aminoacyl-tRNA synthetases.","authors":"Igor Zivkovic, Morana Dulic, Ita Gruic-Sovulj","doi":"10.1002/1873-3468.70098","DOIUrl":"10.1002/1873-3468.70098","url":null,"abstract":"<p><p>Accurate protein synthesis is crucial for life. The key players are aminoacyl-tRNA synthetases (AARSs), which read the genetic code by pairing cognate amino acids and tRNAs. AARSs establish high amino acid selectivity by employing physicochemical limits in molecular recognition. However, chemical and structural resemblance between some amino acids prevents their efficient discrimination by AARSs. In these cases, AARSs hydrolyze the formed non-cognate intermediates or aa-tRNAs to ensure selectivity, establishing complex reaction pathways within the synthetic and editing sites. Understanding AARS mechanisms is crucial for understanding their biology. Here, we review kinetic assays for exploring AARS mechanisms. For each assay, we state the most suitable substrates, product(s) recommended to follow, and, importantly, possible caveats that may lead to the kinetic artefact.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559560","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}
FEBS LettersPub Date : 2025-07-03DOI: 10.1002/1873-3468.70103
{"title":"EXPRESSION OF CONCERN: Inhibition of Endothelial Cell Migration by Cerivastatin, an HMG-CoA Reductase Inhibitor: Contribution to Its Anti-Angiogenic Effect","authors":"","doi":"10.1002/1873-3468.70103","DOIUrl":"10.1002/1873-3468.70103","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN:</b> \u0000 <span>L. Vincent</span>, <span>W. Chen</span>, <span>L. Hong</span>, <span>F. Mirshahi</span>, <span>Z. Mishal</span>, <span>T. Mirshahi-Khorassani</span>, <span>J.-P. Vannier</span>, <span>J. Soria</span>, and <span>C. Soria</span>, “ <span>Inhibition of Endothelial Cell Migration by Cerivastatin, an HMG-CoA Reductase Inhibitor: Contribution to Its Anti-Angiogenic Effect</span>,” <i>FEBS Letters</i> <span>495</span>, no. <span>3</span> (<span>2001</span>): <span>159</span>\u0000 <span>-166</span>, https://doi.org/10.1016/S0014-5793(01)02337-7.</p><p>This Expression of Concern is for the above article, published online on 25 April 2001 in Wiley Online Library (wileyonlinelibrary.com), and has been published by agreement between the journal Editor-in-Chief, Michael Brunner; FEBS Press; and John Wiley and Sons Ltd. The Expression of Concern has been published due to concerns raised by a third party regarding duplicated and rotated image sections within Figure 2 (1A and 4A panels) representing different experimental conditions. A subsequent investigation by the journal team identified further duplications between the panels 1B and 4C of Figure 2. The authors and their institute were informed about the concerns but they remained unresponsive. In the absence of a satisfactory explanation and/or the original raw data, the journal team could not verify the authenticity of these figures and could not exclude that these concerns affect the related conclusions of the article. Therefore, the journal has decided to issue an Expression of Concern to inform and alert the readers.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 15","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552779","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}
FEBS LettersPub Date : 2025-07-02DOI: 10.1002/1873-3468.70100
{"title":"EXPRESSION OF CONCERN: Introgression of a Novel Salt-Tolerant L-Myo-Inositol 1-Phosphate Synthase from Porteresia Coarctata (Roxb.) Tateoka (PcINO1) Confers Salt Tolerance to Evolutionary Diverse Organisms","authors":"","doi":"10.1002/1873-3468.70100","DOIUrl":"10.1002/1873-3468.70100","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: A. Das-Chatterjee, L. Goswami, S. Maitra, K. G. Dastidar, S. Ray, and A. L. Majumder, “Introgression of a Novel Salt-Tolerant L-<i>Myo</i>-Inositol 1-Phosphate Synthase from <i>Porteresia Coarctata</i> (Roxb.) Tateoka (<i>PcINO1</i>) Confers Salt Tolerance to Evolutionary Diverse Organisms,” <i>FEBS Letters</i> 580, no. 16 (2006): 3980-3988, https://doi.org/10.1016/j.febslet.2006.06.033.</p><p>This Expression of Concern is for the above article, published online on 21 June 2006 in Wiley Online Library (wileyonlinelibrary.com), and has been published by agreement between the journal Editor-in-Chief, Michael Brunner; FEBS Press; and John Wiley and Sons Ltd. The Expression of Concern has been published due to concerns raised by a third party regarding highly similar image sections between the 200 mM and 300 mM subpanels of Figure 1A. The authors and their institute were informed about the concerns but they remained unresponsive. In the absence of a satisfactory explanation and/or the original raw data, the journal team could not verify the authenticity of these figures and could not exclude that these concerns affect the related conclusions of the article. Therefore, the journal has decided to issue an Expression of Concern to inform and alert the readers.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 15","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539728","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}
FEBS LettersPub Date : 2025-07-01DOI: 10.1002/1873-3468.70104
Mayuko Yagi, Yuka Hirosawa, Yusaku Sagisaka, Minami Hama, Satoshi Takeda, Jun A. Komano
{"title":"Intron-oriented HTLV-1 integration in an adult T-cell leukemia/lymphoma cell line sustains expression of intact ift81 mRNA","authors":"Mayuko Yagi, Yuka Hirosawa, Yusaku Sagisaka, Minami Hama, Satoshi Takeda, Jun A. Komano","doi":"10.1002/1873-3468.70104","DOIUrl":"10.1002/1873-3468.70104","url":null,"abstract":"<p>The oncogene <i>hbz</i> in human T-cell leukemia virus type 1 (HTLV-1) is encoded on the antisense strand, generating spliced and unspliced transcripts. We investigated splicing regulation in the context of cellular splice donors and the <i>hbz</i> splice acceptor when integrated within the host chromosomal DNA. In ATL cell line ED, the HTLV-1 provirus integrated into the 10th intron of the gene <i>ift81</i>, aligning transcriptionally with <i>ift81</i>. Both genes were actively transcribed, yielding <i>ift81–hbz</i> chimeric mRNA but not <i>hbz–ift81</i>. Splicing efficiency from the 10th exon of <i>ift81</i> to the 2nd exon of <i>hbz</i> was 24.2% at most, suggesting reduced function of <i>hbz</i> splice signals on <i>ift81</i>-driven transcripts. This stochastic regulation may minimize disruption of cellular gene expression by proviral integration, potentially promoting survival of HTLV-1-infected cells and contributing to HTLV-1 pathogenesis.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 18","pages":"2620-2628"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539729","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":"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":"10.1002/1873-3468.70106","url":null,"abstract":"<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 <i>pou5f3</i> 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":"599 15","pages":"2129-2141"},"PeriodicalIF":3.0,"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}
FEBS LettersPub Date : 2025-06-26DOI: 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}