eLife最新文献

{"title":"Negative regulation of miRNA sorting into EVs is mediated by the capacity of RBP PCBP2 to impair the SYNCRIP-dependent miRNA loading.","authors":"Francesco Marocco, Sabrina Garbo, Claudia Montaldo, Alessio Colantoni, Luca Quattrocchi, Gioele Gaboardi, Giovanna Sabarese, Carla Cicchini, Mario Lecce, Alessia Carnevale, Rossella Paolini, Gian Gaetano Tartaglia, Cecilia Battistelli, Marco Tripodi","doi":"10.7554/eLife.105017","DOIUrl":"10.7554/eLife.105017","url":null,"abstract":"<p><p>While it is accepted that extracellular vesicles (EVs)-mediated transfer of microRNAs contributes to intercellular communication, the knowledge about molecular mechanisms controlling the selective and dynamic miRNA-loading in EVs is still limited to few specific RNA-binding proteins interacting with sequence determinants. Moreover, although mutagenesis analysis demonstrated the presence/function of specific intracellular retention motifs, the interacting protein/s remained unknown. Here, PCBP2 was identified as a direct interactor of an intracellular retention motif: CLIP coupled to RNA pull-down and proteomic analysis demonstrated that it binds to miRNAs embedding this motif and mutagenesis proved the binding specificity. Notably, PCBP2 binding requires SYNCRIP, a previously characterized miRNA EV-loader as indicated by SYNCRIP knock-down. SYNCRIP and PCBP2 may contemporarily bind to miRNAs as demonstrated by EMSA assays and PCBP2 knock-down causes EV loading of intracellular microRNAs. This evidence highlights that multiple proteins/miRNA interactions govern miRNA compartmentalization and identifies PCBP2 as a dominant inhibitor of SYNCRIP function in murine hepatocytes.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552684","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":"Searching for druggable targets.","authors":"Lana Heganovic, Luiz F M Passalacqua","doi":"10.7554/eLife.107757","DOIUrl":"10.7554/eLife.107757","url":null,"abstract":"<p><p>A strategy that analyzes the structural properties of RNA could help identify regions that are promising targets for antiviral drugs.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539594","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":"Exploiting functional regions in the viral RNA genome as druggable entities.","authors":"Dehua Luo, Yingge Zheng, Zhiyuan Huang, Zi Wen, Lijun Guo, Yingxiang Deng, Qingling Li, Yuqing Bai, Shozeb Haider, Dengguo Wei","doi":"10.7554/eLife.103923","DOIUrl":"10.7554/eLife.103923","url":null,"abstract":"<p><p>RNA-targeting compounds or small interfering RNAs (siRNAs) offer a potent means to control viral infections. An essential prerequisite for their design depends on identifying conserved and functional viral RNA structures in cells. Techniques that probe RNA structures in situ have recently been developed including SHAPE-MaP, which has been helpful in the analysis of secondary structures of RNA. In this study, we report on the application of SHAPE-MaP to the porcine epidemic diarrhea virus RNA genome to categorize different functional regions, including potential quadruplex-forming sequence and target sites of siRNA. Our results show that these structures can be exploited to inhibit viral proliferation and that SHAPE-MaP is an effective method to identify secondary structures in RNA genomes.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539574","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":"Hunger shifts attention and attribute weighting in dietary choice.","authors":"Jennifer March, Sebastian Gluth","doi":"10.7554/eLife.103736","DOIUrl":"10.7554/eLife.103736","url":null,"abstract":"<p><p>Hunger is a biological drive which can promote unhealthy dietary decisions. Yet, the cognitive mechanisms underlying this effect, and in particular the interactive role of attention and choice processes, remain elusive. To address this gap, we conducted an eye-tracking experiment, in which 70 participants completed a multi-attribute food choice task in hungry and sated states. Confirming our preregistered hypotheses, participants' preference for tasty over healthy food items was amplified by hunger. Attention mediated this influence of hunger, as hungry participants focused more on tasty options, leading them to make less healthy decisions. Rigorous model comparisons revealed that an extension of the recently proposed multi-attribute attentional drift diffusion model best explained choice and response times. According to this model, hunger did not only increase the relative taste compared to health weight, but it also increased the fixation-related discounting of health but not taste information. Our results suggest that the cognitive mechanisms underlying unhealthy dietary decisions under hunger are characterized by a nuanced interplay between attention and the significance assigned to the options' underlying attributes.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539575","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":"Inference technique for the synaptic conductances in rhythmically active networks and application to respiratory central pattern generation circuits.","authors":"Yaroslav Molkov, Anke Borgmann, Hidehiko Koizumi, Noriyuki Hama, Ruli Zhang, Jeffrey Smith","doi":"10.7554/eLife.101959","DOIUrl":"10.7554/eLife.101959","url":null,"abstract":"<p><p>Unraveling synaptic interactions between excitatory and inhibitory interneurons within rhythmic neural circuits, such as central pattern generation (CPG) circuits for rhythmic motor behaviors, is critical for deciphering circuit interactions and functional architecture, which is a major problem for understanding how neural circuits operate. Here, we present a general method for extracting and separating patterns of inhibitory and excitatory synaptic conductances at high temporal resolution from single neuronal intracellular recordings in rhythmically active networks. These post-synaptic conductances reflect the combined synaptic inputs from the key interacting neuronal populations and can reveal the functional connectome of the active circuits. To illustrate the applicability of our analytic technique, we employ our method to infer the synaptic conductance profiles in identified rhythmically active interneurons within key microcircuits of the mammalian (mature rat) brainstem respiratory CPG and provide a perspective on how our approach can resolve the functional interactions and circuit organization of these interneuron populations. We demonstrate the versatility of our approach, which can be applied to any other rhythmic circuits where conditions allow for neuronal intracellular recordings.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539576","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":"Human eIF2A has a minimal role in translation initiation and in uORF-mediated translational control in HeLa cells.","authors":"Mykola Roiuk, Marilena Neff, Aurelio A Teleman","doi":"10.7554/eLife.105311","DOIUrl":"10.7554/eLife.105311","url":null,"abstract":"<p><p>Translation initiation in eukaryotes requires a 40 S ribosome loaded with initiator tRNA which scans for an initiation codon. The initiator tRNA is usually recruited to the ribosome as part of a ternary complex composed of initiator tRNA, eIF2, and GTP. Although initiator tRNA recruitment was originally ascribed to another factor, eIF2A, it was later disproven and shown to occur via eIF2. Nonetheless, eIF2A is still considered a translation initiation factor because it binds the ribosome and shows genetic interactions with other initiation factors such as eIF4E. The exact function of eIF2A during translation initiation, however, remains unclear. Here, we use ribosome profiling and luciferase reporter assays to systematically test in HeLa cells the role of eIF2A in translation initiation, including translation of upstream ORFs. Since eIF2A is thought to take over the function of eIF2 when eIF2 is inhibited, we also test conditions where the integrated stress response is activated. In none of our assays, however, could we detect a role of eIF2A in translation initiation. It is possible that eIF2A plays a role in translation regulation in specific conditions that we have not tested here, or that it plays a role in a different aspect of RNA biology.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539592","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":"Planar cell polarity coordination in a cnidarian embryo provides clues to animal body axis evolution.","authors":"Julie Uveira, Antoine Donati, Marvin Léria, Marion Lechable, François Lahaye, Christine Vesque, Evelyn Houliston, Tsuyoshi Momose","doi":"10.7554/eLife.104508","DOIUrl":"10.7554/eLife.104508","url":null,"abstract":"<p><p>Body axis specification is a crucial event in animal embryogenesis and was an essential evolutionary innovation for founding the animal kingdom. This process involves two distinct components that coordinate to establish the spatial organisation of the embryo: initiation of cascades of regionalised gene expression and orientation of morphogenetic processes such as body elongation. Intense interest in the first component has revealed Wnt/β-catenin signalling as ancestrally responsible for initiating regional gene expression, but the evolutionary origin of oriented morphogenesis has received little attention. Here, by addressing the cell and morphological basis of body axis development in embryos of the cnidarian <i>Clytia hemisphaerica</i>, we have uncovered a simple and likely ancestral coordination mechanism between Wnt/β-catenin signalling and directed morphogenesis. We show that the ligand Wnt3, known to initiate oral gene expression via localised Wnt/β-catenin pathway activation, also has a key β-catenin-independent role in globally orienting planar cell polarity (PCP) to direct morphogenesis along the oral-aboral axis. This PCP orientation occurs in two distinct steps: local orientation by Wnt3 and global propagation by conserved core PCP protein interactions along the body axis. From these findings, we propose novel scenarios for PCP-driven symmetry-breaking underlying the emergence of the animal body plan.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539593","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":"Structural insights into heterohexameric assembly of epilepsy-related ligand-receptor complex LGI1-ADAM22.","authors":"Takayuki Yamaguchi, Kei Okatsu, Masato Kubota, Ayuka Mitsumori, Atsushi Yamagata, Yuko Fukata, Masaki Fukata, Mikihiro Shibata, Shuya Fukai","doi":"10.7554/eLife.105918","DOIUrl":"10.7554/eLife.105918","url":null,"abstract":"<p><p>Leucine-rich glioma-inactivated 1 protein (LGI1) is a secreted neuronal protein consisting of the N-terminal leucine-rich repeat (LRR) and C-terminal epitempin-repeat (EPTP) domains. LGI1 is linked to epilepsy, a neurological disorder that can be caused by genetic mutations of genes regulating neuronal excitability (e.g. voltage- or ligand-gated ion channels). ADAM22 is a membrane receptor that binds to LGI1 extracellularly and interacts with AMPA-type glutamate receptors via PSD-95 intracellularly to maintain normal synaptic signal transmission. Structural analysis of the LGI1-ADAM22 complex is important for understanding the molecular mechanism of epileptogenesis and developing new therapies against epilepsy. We previously reported the crystal structure of a 2:2 complex consisting of two molecules of LGI1 and two molecules of the ADAM22 ectodomain (ECD), which is suggested to bridge neurons across the synaptic cleft. On the other hand, multiangle light scattering, small-angle X-ray scattering, and cryo-electron microscopy (cryo-EM) analyses have suggested the existence of a 3:3 complex consisting of three molecules of LGI1 and three molecules of ADAM22. In the previous cryo-EM analysis, many observed particles were in a dissociated state, making it difficult to determine the three-dimensional (3D) structure of the 3:3 complex. In this study, we stabilized the 3:3 LGI1-ADAM22_ECD complex using chemical cross-linking and determined the cryo-EM structures of the LGI1_LRR-LGI1_EPTP-ADAM22_ECD and 3:3 LGI1-ADAM22_ECD complexes at 2.78 Å and 3.79 Å resolutions, respectively. Furthermore, high-speed atomic force microscopy (HS-AFM) visualized the structural features and flexibility of the 3:3 LGI1-ADAM22_ECD complex in solution. We discuss new insights into the interaction modes of the LGI1-ADAM22 higher-order complex and the structural properties of the 3:3 LGI1-ADAM22 complex.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552685","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":"Current insights into insect immune memory.","authors":"Gabriela Krejčová, Adam Bajgar","doi":"10.7554/eLife.105011","DOIUrl":"10.7554/eLife.105011","url":null,"abstract":"<p><p>Traditionally, insects have been thought to be entirely dependent on their innate immune system, which has little capacity for the acquisition of experience from previous infections. However, much experimental evidence has challenged this view, showing that insects can develop long-term, pathogen-specific immune memory, which in some cases can be transmitted to offspring. Although significant progress has been made in this area, the underlying mechanism is still not fully understood, and a number of fundamental questions remain unanswered. In this review, we present an overview of documented cases of insect immune memory and summarize the experimental evidence in support of the prevailing hypotheses on the mechanism of antiviral and antibacterial immune memory in insects. We also highlight key questions that remain unanswered and discuss <i>Drosophila melanogaster</i> as a powerful model organism for investigating the mechanisms of innate immune memory formation. Finally, we evaluate the significance of this research and explore the potential for insect vaccination.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539591","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":"A neuromorphic model of active vision shows how spatiotemporal encoding in lobula neurons can aid pattern recognition in bees.","authors":"HaDi MaBouDi, Mark Roper, Marie-Geneviève Guiraud, Mikko Juusola, Lars Chittka, James A R Marshall","doi":"10.7554/eLife.89929","DOIUrl":"10.7554/eLife.89929","url":null,"abstract":"<p><p>Bees' remarkable visual learning abilities make them ideal for studying active information acquisition and representation. Here, we develop a biologically inspired model to examine how flight behaviours during visual scanning shape neural representation in the insect brain, exploring the interplay between scanning behaviour, neural connectivity, and visual encoding efficiency. Incorporating non-associative learning-adaptive changes without reinforcement-and exposing the model to sequential natural images during scanning, we obtain results that closely match neurobiological observations. Active scanning and non-associative learning dynamically shape neural activity, optimising information flow and representation. Lobula neurons, crucial for visual integration, self-organise into orientation-selective cells with sparse, decorrelated responses to orthogonal bar movements. They encode a range of orientations, biased by input speed and contrast, suggesting co-evolution with scanning behaviour to enhance visual representation and support efficient coding. To assess the significance of this spatiotemporal coding, we extend the model with circuitry analogous to the mushroom body, a region linked to associative learning. The model demonstrates robust performance in pattern recognition, implying a similar encoding mechanism in insects. Integrating behavioural, neurobiological, and computational insights, this study highlights how spatiotemporal coding in the lobula efficiently compresses visual features, offering broader insights into active vision strategies and bio-inspired automation.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526924","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}