Communications Biology最新文献

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The medial and lateral orbitofrontal cortex jointly represent the cognitive map of task space.
IF 5.2 1区 生物学
Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07588-w
Liwei Tan, Yidan Qiu, Lixin Qiu, Shuting Lin, Jinhui Li, Jiajun Liao, Yuting Zhang, Wei Zou, Ruiwang Huang
{"title":"The medial and lateral orbitofrontal cortex jointly represent the cognitive map of task space.","authors":"Liwei Tan, Yidan Qiu, Lixin Qiu, Shuting Lin, Jinhui Li, Jiajun Liao, Yuting Zhang, Wei Zou, Ruiwang Huang","doi":"10.1038/s42003-025-07588-w","DOIUrl":"10.1038/s42003-025-07588-w","url":null,"abstract":"<p><p>A cognitive map is an internal model of the world's causal structure, crucial for adaptive behaviors. The orbitofrontal cortex (OFC) is central node to decision-making and cognitive map representation. However, it remains unclear how the medial OFC (mOFC) and lateral OFC (lOFC) contribute to the formation of cognitive maps in humans. By performing a multi-step sequential task and multivariate analyses of functional magnetic resonance imaging (fMRI) data, we found that the mOFC and lOFC play complementary but dissociable roles in this process. Specifically, the mOFC represents all hidden task state components. The lOFC and dorsolateral prefrontal cortex (dlPFC) encode abstract rules governing structure knowledge across task states. Furthermore, the two orbitofrontal subregions are functionally connected to share state-hidden information for constructing a representation of the task structure. Collectively, these findings provide an account that can increase our understanding of how the brain constructs abstract cognitive maps in a task-relevant space.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"163"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122264","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}
引用次数: 0
Optimized gene transduction in human lung organoids: A high-efficiency method for advanced research applications.
IF 5.2 1区 生物学
Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07461-w
Jasmin Khateeb, Jady Liang, Yuchong Li, Thenuka Thanabalasingam, Julie Khang, Mirjana Jerkic, Giovanna Pellecchia, Bhooma Thiruv, Ya-Wen Chen, Ori Rotstein, Arthur S Slutsky, Haibo Zhang
{"title":"Optimized gene transduction in human lung organoids: A high-efficiency method for advanced research applications.","authors":"Jasmin Khateeb, Jady Liang, Yuchong Li, Thenuka Thanabalasingam, Julie Khang, Mirjana Jerkic, Giovanna Pellecchia, Bhooma Thiruv, Ya-Wen Chen, Ori Rotstein, Arthur S Slutsky, Haibo Zhang","doi":"10.1038/s42003-025-07461-w","DOIUrl":"10.1038/s42003-025-07461-w","url":null,"abstract":"<p><p>Human induced pluripotent stem cell (iPSC)-derived lung organoids, engineered to carry targeted genes, offer a robust platform for investigating mechanistic insights in lung research. Although lentiviral vectors (LVVs) are highly effective for stable expression due to their integrative properties, achieving efficient transduction in human iPSC-derived lung organoids poses a significant technical challenge, likely due to the complex structure of these organoids. In this study, we optimized a method to enhance LVV transduction efficiency by physically disrupting the organoids to increase surface area, followed by spinoculation to apply shear force during cell dissociation. This approach, combined with the use of an optimized culture medium, significantly improved transduction efficiency. The success of this method was validated at both the gene and protein levels using single-cell RNA sequencing (scRNA-seq) and various cellular and molecular assays. Our optimized transduction protocol may provide a valuable tool for investigating specific cellular and molecular mechanisms in development and disease models using human iPSCs-derived lung organoids.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"164"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122261","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}
引用次数: 0
Accelerating biopharmaceutical cell line selection with label-free multimodal nonlinear optical microscopy and machine learning.
IF 5.2 1区 生物学
Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07596-w
Jindou Shi, Alexander Ho, Corey E Snyder, Eric J Chaney, Janet E Sorrells, Aneesh Alex, Remben Talaban, Darold R Spillman, Marina Marjanovic, Minh Doan, Gary Finka, Steve R Hood, Stephen A Boppart
{"title":"Accelerating biopharmaceutical cell line selection with label-free multimodal nonlinear optical microscopy and machine learning.","authors":"Jindou Shi, Alexander Ho, Corey E Snyder, Eric J Chaney, Janet E Sorrells, Aneesh Alex, Remben Talaban, Darold R Spillman, Marina Marjanovic, Minh Doan, Gary Finka, Steve R Hood, Stephen A Boppart","doi":"10.1038/s42003-025-07596-w","DOIUrl":"10.1038/s42003-025-07596-w","url":null,"abstract":"<p><p>The selection of high-performing cell lines is crucial for biopharmaceutical production but is often time-consuming and labor-intensive. We investigated label-free multimodal nonlinear optical microscopy for non-perturbative profiling of biopharmaceutical cell lines based on their intrinsic molecular contrast. Employing simultaneous label-free autofluorescence multiharmonic (SLAM) microscopy with fluorescence lifetime imaging microscopy (FLIM), we characterized Chinese hamster ovary (CHO) cell lines at early passages (0-2). A machine learning (ML)-assisted analysis pipeline leveraged high-dimensional information to classify single cells into their respective lines. Remarkably, the monoclonal cell line classifiers achieved balanced accuracies exceeding 96.8% as early as passage 2. Correlation features and FLIM modality played pivotal roles in early classification. This integrated optical bioimaging and machine learning approach presents a promising solution to expedite cell line selection process while ensuring identification of high-performing biopharmaceutical cell lines. The techniques have potential for broader single-cell characterization applications in stem cell research, immunology, cancer biology and beyond.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"157"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122346","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}
引用次数: 0
Arginine methyltransferase PRMT1 promotes ferroptosis through EGR1/GLS2 axis in sepsis-related acute lung injury.
IF 5.2 1区 生物学
Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07531-z
Min Li, Longhui Hu, Qiao Ke, Zhao Li, Chujun Ruan, Hanjing Lu, Xiaoran Liu
{"title":"Arginine methyltransferase PRMT1 promotes ferroptosis through EGR1/GLS2 axis in sepsis-related acute lung injury.","authors":"Min Li, Longhui Hu, Qiao Ke, Zhao Li, Chujun Ruan, Hanjing Lu, Xiaoran Liu","doi":"10.1038/s42003-025-07531-z","DOIUrl":"10.1038/s42003-025-07531-z","url":null,"abstract":"<p><p>Acute lung injury (ALI), a frequent and severe complication of sepsis, is associated with significant mortality rates. Previous studies indicated that GLS2 plays a key role in promoting ferroptosis. However, its underlying mechanisms remain unclear. Here we show, there were elevated ferroptosis and increased expression levels of protein arginine methyltransferase 1 (PRMT1), early growth response 1 (EGR1), and glutaminase 2 (GLS2) in both in vitro and in vivo ALI models. Additionally, EGR1 was found to induce the transcription of GLS2, thereby promoting ferroptosis. We also discovered that the protein level of EGR1 was increased through enhanced stability, facilitated by PRMT1-mediated arginine methylation, and reduced ubiquitination degradation regulated by neural precursor cell expressed developmentally down-regulated protein 4 like (NEDD4L). The in vivo results confirmed that the knockdown of PRMT1 suppressed ferroptosis via the EGR1/GLS2 axis. Our findings suggest that PRMT1-mediated stabilization of EGR1 promoted sepsis induced ALI via GLS2, highlighting the therapeutic potential of targeting PRMT1 or EGR1 in the treatment of sepsis-induced ALI.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"159"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122347","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}
引用次数: 0
Warming alters plankton body-size distributions in a large field experiment.
IF 5.2 1区 生物学
Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-024-07380-2
Dania Albini, Emma Ransome, Alex J Dumbrell, Samraat Pawar, Eoin J O'Gorman, Thomas P Smith, Thomas Bell, Michelle C Jackson, Guy Woodward
{"title":"Warming alters plankton body-size distributions in a large field experiment.","authors":"Dania Albini, Emma Ransome, Alex J Dumbrell, Samraat Pawar, Eoin J O'Gorman, Thomas P Smith, Thomas Bell, Michelle C Jackson, Guy Woodward","doi":"10.1038/s42003-024-07380-2","DOIUrl":"10.1038/s42003-024-07380-2","url":null,"abstract":"<p><p>The threat of climate change has renewed interest in the responses of communities and ecosystems to warming, with changes in size spectra expected to signify fundamental shifts in the structure and dynamics of these multispecies systems. While substantial empirical evidence has accumulated in recent years on such changes, we still lack general insights due to a limited coverage of warming scenarios that span spatial and temporal scales of relevance to natural systems. We addressed this gap by conducting an extensive freshwater mesocosm experiment across 36 large field mesocosms exposed to intergenerational warming treatments of up to +8 °C above ambient levels. We found a nonlinear decrease in the overall mean body size of zooplankton with warming, with a 57% reduction at +8 °C. This pattern was broadly consistent over two tested seasons and major taxonomic groups. We also detected some breakpoints in the community-level size-temperature relationship, indicating that the system's response shifts noticeably above a certain level of warming. These results underscore the need to capture intergenerational responses to large gradients in warming at appropriate scales in time and space in order to better understand the effects of warming on natural communities and ecosystems.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"162"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122265","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}
引用次数: 0
Devaluing memories of reward: a case for dopamine.
IF 5.2 1区 生物学
Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-024-07440-7
Benjamin R Fry, Nicolette Russell, Victoria Fex, Bing Mo, Nathan Pence, Joseph A Beatty, Fredric P Manfredsson, Brandon A Toth, Christian R Burgess, Samuel Gershman, Alexander W Johnson
{"title":"Devaluing memories of reward: a case for dopamine.","authors":"Benjamin R Fry, Nicolette Russell, Victoria Fex, Bing Mo, Nathan Pence, Joseph A Beatty, Fredric P Manfredsson, Brandon A Toth, Christian R Burgess, Samuel Gershman, Alexander W Johnson","doi":"10.1038/s42003-024-07440-7","DOIUrl":"10.1038/s42003-024-07440-7","url":null,"abstract":"<p><p>Midbrain dopamine cells encode differences in predictive and expected value to support learning through reward prediction error. Recent findings have questioned whether reward prediction error can fully account for dopamine function and suggest a more complex role for dopamine in encoding detailed features of the reward environment. In this series of studies, we describe a novel role for dopamine in devaluing sensory features of reward. Mesencephalic dopamine cells activated during a mediated devaluation phase were later chemogenetically reactivated. This retrieval of the devalued reward memory elicited a reduction in the hedonic evaluation of sucrose reward. Through optogenetic and chemogenetic manipulations, we confirm dopamine cells are both sufficient and necessary for mediated devaluation, and retrieval of these memories reflected dopamine release in the nucleus accumbens. Consistent with our computational modeling data, our findings indicate a critical role for dopamine in encoding predictive representations of the sensory features of reinforcement. Overall, we elucidate a novel role for dopamine function in mediated devaluation and illuminate a more elaborate framework through which dopamine encodes reinforcement signals.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"161"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122259","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}
引用次数: 0
Who arrived first? Priority effects on Candida albicans and Pseudomonas aeruginosa dual biofilms.
IF 5.2 1区 生物学
Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07609-8
Betsy V Arévalo-Jaimes, Joana Admella, Eduard Torrents
{"title":"Who arrived first? Priority effects on Candida albicans and Pseudomonas aeruginosa dual biofilms.","authors":"Betsy V Arévalo-Jaimes, Joana Admella, Eduard Torrents","doi":"10.1038/s42003-025-07609-8","DOIUrl":"10.1038/s42003-025-07609-8","url":null,"abstract":"<p><p>Historical processes in community assembly, such as species arrival order, influence interactions, causing priority effects. Candida albicans and Pseudomonas aeruginosa often co-occur in biofilm-based infections of the skin, lungs, and medical devices. Their predominantly antagonistic relationship involves complex physical and chemical interactions. However, the presence and implications of priority effects among these microorganisms remain largely unexplored. Here, we investigate the presence and impact of priority effect in dual-species biofilms using clinical isolates. By varying inoculation order, we observe significant changes in biofilm composition, structure, virulence, and antimicrobial susceptibility. The first colonizer has an advantage for surface colonization. Consecutive colonization increases biofilm virulence and negates C. albicans' protective effect on P. aeruginosa PAET1 against meropenem treatment. Finally, we propose N-acetylcysteine as an adjuvant for treating C. albicans and P. aeruginosa interkingdom infections, working independently of priority effects.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"160"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122266","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}
引用次数: 0
Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity.
IF 5.2 1区 生物学
Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07572-4
Wassim Daher, Vincent Le Moigne, Yara Tasrini, Shweta Parmar, Danielle L Sexton, John Jairo Aguilera-Correa, Valentin Berdal, Elitza I Tocheva, Jean-Louis Herrmann, Laurent Kremer
{"title":"Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity.","authors":"Wassim Daher, Vincent Le Moigne, Yara Tasrini, Shweta Parmar, Danielle L Sexton, John Jairo Aguilera-Correa, Valentin Berdal, Elitza I Tocheva, Jean-Louis Herrmann, Laurent Kremer","doi":"10.1038/s42003-025-07572-4","DOIUrl":"10.1038/s42003-025-07572-4","url":null,"abstract":"<p><p>Type VII secretion systems participate in protein export, virulence, conjugation, and metabolic regulation. Five subtypes (ESX-1 to ESX-5) exist, each with specific roles and well-characterized secretion profiles in various mycobacterial species. Mycobacterium abscessus, encodes only ESX-3 and ESX-4. Here, single and double M. abscessus mutants lacking the main ATPases EccC3 and EccC4 were used to define ESX-3 and ESX-4 contributions to substrate secretion and virulence. Our results demonstrate that EsxG/H secretion depends entirely on ESX-3, whereas both ESX-3 and ESX-4 secrete EsxU/T. Furthermore, two newly identified PE/PPE substrates (MAB_0046/MAB_0047) require ESX-3 for secretion. Functional complementation restored secretion and revealed subpolar localization of these systems. Macrophage infections showed that ESX-3 and ESX-4 contribute to bacterial internalization, phagosomal escape, and intracellular survival. In mice, infections with eccC3- and/or eccC4-deletion mutants resulted in complete survival and reduced bacterial loads in the lungs. These findings demonstrate that both ESX systems drive M. abscessus pathogenicity.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"166"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122258","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}
引用次数: 0
Mapping and modeling age-related changes in intrinsic neural timescales.
IF 5.2 1区 生物学
Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07517-x
Kaichao Wu, Leonardo L Gollo
{"title":"Mapping and modeling age-related changes in intrinsic neural timescales.","authors":"Kaichao Wu, Leonardo L Gollo","doi":"10.1038/s42003-025-07517-x","DOIUrl":"10.1038/s42003-025-07517-x","url":null,"abstract":"<p><p>Intrinsic timescales of brain regions exhibit heterogeneity, escalating with hierarchical levels, and are crucial for the temporal integration of external stimuli. Aging, often associated with cognitive decline, involves progressive neuronal and synaptic loss, reshaping brain structure and dynamics. However, the impact of these structural changes on temporal coding in the aging brain remains unclear. We mapped intrinsic timescales and gray matter volume (GMV) using magnetic resonance imaging (MRI) in young and elderly adults. We found shorter intrinsic timescales across multiple large-scale functional networks in the elderly cohort, and a significant positive association between intrinsic timescales and GMV. Additionally, age-related decline in performance on visual discrimination tasks was linked to a reduction in intrinsic timescales in the cuneus. To explain these age-related shifts, we developed an age-dependent spiking neuron network model. In younger subjects, brain regions were near a critical branching regime, while regions in elderly subjects had fewer neurons and synapses, pushing the dynamics toward a subcritical regime. The model accurately reproduced the empirical results, showing longer intrinsic timescales in young adults due to critical slowing down. Our findings reveal how age-related structural brain changes may drive alterations in brain dynamics, offering testable predictions and informing possible interventions targeting cognitive decline.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"167"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122260","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}
引用次数: 0
A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA.
IF 5.2 1区 生物学
Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07600-3
Man Lu, Zhiqiang Cao, Luoan Xiong, Hongying Deng, Kangkang Ma, Ning Liu, Yanding Qin, Shen-Bo Chen, Jun-Hu Chen, Yao Li, Yijin Liu, Zhongbo Yu
{"title":"A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA.","authors":"Man Lu, Zhiqiang Cao, Luoan Xiong, Hongying Deng, Kangkang Ma, Ning Liu, Yanding Qin, Shen-Bo Chen, Jun-Hu Chen, Yao Li, Yijin Liu, Zhongbo Yu","doi":"10.1038/s42003-025-07600-3","DOIUrl":"10.1038/s42003-025-07600-3","url":null,"abstract":"<p><p>Ribozymes, widely found in prokaryotes and eukaryotes, target nucleic acids and can be engineered as biotechnical tools or for gene regulation or immune therapy. Among them, hammerhead is the smallest and best characterized ribozyme. However, the structure and biochemical data of ribozymes have been disagreed on, making the understanding of its catalysis mechanism a longstanding issue. Particularly, the role of conformational dynamics in ribozyme catalysis remains elusive. Here, we use single-molecule magnetic tweezers to reveal a concerted catalysis mechanism of mechanical conformational selection for a mini hammerhead ribozyme against a viral RNA sequence from the SARS-CoV-2. We identify a conformational set containing five mechanical conformers of the mini ribozyme, where magnesium ions select the active one. Our results are supported by molecular dynamics simulations. Our understanding of the RNA catalytic mechanism will be beneficial for ribozyme's biotechnological applications and as potential therapeutics against RNA viruses.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"165"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122345","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}
引用次数: 0
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