Proceedings of the National Academy of Sciences of the United States of America最新文献

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Disorder-driven non-Anderson transition in a Weyl semimetal. Weyl半金属中无序驱动的非anderson跃迁。
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-09 DOI: 10.1073/pnas.2508569122
Cong Li,Yang Wang,Jianfeng Zhang,Hongxiong Liu,Wanyu Chen,Guowei Liu,Hanbin Deng,Timur K Kim,Craig Polley,Balasubramanian Thiagarajan,Jiaxin Yin,Youguo Shi,Tao Xiang,Oscar Tjernberg
{"title":"Disorder-driven non-Anderson transition in a Weyl semimetal.","authors":"Cong Li,Yang Wang,Jianfeng Zhang,Hongxiong Liu,Wanyu Chen,Guowei Liu,Hanbin Deng,Timur K Kim,Craig Polley,Balasubramanian Thiagarajan,Jiaxin Yin,Youguo Shi,Tao Xiang,Oscar Tjernberg","doi":"10.1073/pnas.2508569122","DOIUrl":"https://doi.org/10.1073/pnas.2508569122","url":null,"abstract":"For several decades, it was widely believed that a noninteracting disordered electronic system could only undergo an Anderson metal-insulator transition due to Anderson localization. However, numerous recent theoretical works have predicted the existence of a disorder-driven non-Anderson phase transition that differs from Anderson localization. The frustration lies in the fact that this non-Anderson disorder-driven transition has not yet been experimentally demonstrated in any system. Here, using angle-resolved photoemission spectroscopy, we present a case study of observing the non-Anderson disorder-driven transition by visualizing the electronic structure of the Weyl semimetal NdAlSi on surfaces with varying amounts of disorder. Our observations reveal that strong disorder can effectively suppress all surface states in the Weyl semimetal NdAlSi, including the topological surface Fermi arcs. This disappearance of surface Fermi arcs is associated with the vanishing of the topological invariant, indicating a quantum phase transition from a Weyl semimetal to a diffusive metal. These observations provide direct experimental evidence of the non-Anderson disorder-driven transition occurring in real quantum systems, a finding long anticipated by theoretical physicists.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"60 1","pages":"e2508569122"},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Platelets engage mast cells in a bilateral IL-33-driven feed-forward loop. 血小板在双侧il -33驱动的前馈回路中与肥大细胞结合。
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-09 DOI: 10.1073/pnas.2512193122
Airi Nishida,Jun Nagai,Madeline Hastings,Kendall Zaleski,Marie Sasaki,Omar Samir,Juying Lai,Sofia A Marshall,Hiroaki Hayashi,Sreyashi Majumdar,Kinan Alhallak,Chunli Feng,Tao Liu,Joshua A Boyce
{"title":"Platelets engage mast cells in a bilateral IL-33-driven feed-forward loop.","authors":"Airi Nishida,Jun Nagai,Madeline Hastings,Kendall Zaleski,Marie Sasaki,Omar Samir,Juying Lai,Sofia A Marshall,Hiroaki Hayashi,Sreyashi Majumdar,Kinan Alhallak,Chunli Feng,Tao Liu,Joshua A Boyce","doi":"10.1073/pnas.2512193122","DOIUrl":"https://doi.org/10.1073/pnas.2512193122","url":null,"abstract":"Platelets amplify type 2 inflammation (T2I) through incompletely understood mechanisms. Depletion of platelets markedly attenuated mast cell (MC) activation in a model of aspirin exacerbated respiratory disease (AERD) that depends on IL-33 and cysteinyl leukotrienes (cysLTs). We demonstrate an IL-33-driven feed-forward loop between platelets and MCs. IL-33 neutralization prevented increases in cysLTs and CXCL7, a platelet activation marker, in bronchoalveolar lavage (BAL) fluid from AERD-like mice in response to aspirin challenges. BAL fluid concentrations of PGD2 correlated strongly with both CXCL7 and MC tryptase in subjects with severe asthma. Platelets amplified PGD2 and LTC4 productions by IL-33-stimulated mouse bone marrow-derived MCs (BMMCs), which induced release of CXCL7 and expression of CD62P by platelets. Deletions of MC-specific LTC4 or platelet-specific type 2 cysLT receptor (CysLT2R) completely eliminated both platelet activation and the amplification of PGD2 and LTC4 generation by MCs. Platelet-derived ADP/ATP and MC-associated P2Y1 receptors were essential. These findings identify an innate immune pathway involving MC-platelet interplay that may drive IL-33-dependent immunopathology in asthma.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"112 1","pages":"e2512193122"},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chimeric RNA isoforms generated by diverse mechanisms from two C-type lectins modulate innate immunity in arthropods. 两种c型凝集素通过不同机制产生的嵌合RNA亚型调节节肢动物的先天免疫。
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-09 DOI: 10.1073/pnas.2518148122
Ying Huang,Xin Huang,Li-Hua Zhang,Qian Ren
{"title":"Chimeric RNA isoforms generated by diverse mechanisms from two C-type lectins modulate innate immunity in arthropods.","authors":"Ying Huang,Xin Huang,Li-Hua Zhang,Qian Ren","doi":"10.1073/pnas.2518148122","DOIUrl":"https://doi.org/10.1073/pnas.2518148122","url":null,"abstract":"Chimeric RNA formation represents a critical mechanism for expanding protein functional diversity, yet its role in invertebrate immune adaptation remains poorly characterized. Here, we report that two C-type lectin genes (MnLec2 and MnLec3) from distinct genomic loci in the oriental river prawn Macrobrachium nipponense undergo positionally flexible chimeric RNA formation via alternative trans-splicing and transcriptional slippage, generating 11 structurally diverse chimeric isoforms (MnLec1, MnLec4-13) with bidirectional exon joining. Crucially, pathogen challenges reprogram chimeric RNA frequencies to shift immune equilibrium, universally suppressing detrimental MnLec9 while promoting protective MnLec7 formation. Functional dissection confirms dual-action pathogen suppression, recombinant MnLec7 (rMnLec7) suppresses white spot syndrome virus replication by upregulating antimicrobial peptides and RNAi effectors, while accelerating Vibrio parahaemolyticus clearance and improving survival. Conversely, suppression of MnLec9 removes its immunosuppressive activity, synergistically enhancing host defense. This coordinated isoform rebalancing enables effective pathogen clearance. Thus, positional flexibility in chimeric RNA formation generates antagonistic isoforms that maintain immune homeostasis and deploy targeted defense upon infection, revealing an adaptive transcriptional strategy in arthropods.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"28 1","pages":"e2518148122"},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Electing amateur politicians reduces cross-party collaboration. 选举业余政客减少了跨党派合作。
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-09 DOI: 10.1073/pnas.2519787122
Rachel Porter,Jeffrey J Harden,Mackenzie R Dobson
{"title":"Electing amateur politicians reduces cross-party collaboration.","authors":"Rachel Porter,Jeffrey J Harden,Mackenzie R Dobson","doi":"10.1073/pnas.2519787122","DOIUrl":"https://doi.org/10.1073/pnas.2519787122","url":null,"abstract":"Public trust in democratic institutions has dropped to historic lows, prompting electorates in major democracies to turn to \"amateur\" politicians with the expectation that these political outsiders will cut through stalemates to deliver policy results. Amateurs are often seen as pragmatic \"doers,\" but also uncompromising, a combination at odds with governing systems where legislative progress depends on cross-party coalitions. Using the US Congress as a critical case, we evaluate these competing expectations by linking over four decades of election data with 2.2 million bill (co)sponsorship records. We find that electing amateurs intensifies partisan divisions: Districts that send amateurs to Congress yield representatives who attract fewer opposing-party collaborators to their bills and less often support other-party legislation. Our results suggest that amateurs are unlikely to deliver on their promise for pragmatic governance, as they resist or undervalue the compromises essential to lawmaking.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"114 1","pages":"e2519787122"},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Turning the FeFe hydrogenase from Clostridium beijerinckii into an efficient H2 oxidation catalyst using a redox-active matrix. 利用氧化还原活性基质将贝氏梭菌的铁氢化酶转化为高效的H2氧化催化剂。
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-09 DOI: 10.1073/pnas.2514698122
Dawit T Filmon,Jan Jaenecke,Martin Winkler,Vincent Fourmond,Christophe Léger,Nicolas Plumeré
{"title":"Turning the FeFe hydrogenase from Clostridium beijerinckii into an efficient H2 oxidation catalyst using a redox-active matrix.","authors":"Dawit T Filmon,Jan Jaenecke,Martin Winkler,Vincent Fourmond,Christophe Léger,Nicolas Plumeré","doi":"10.1073/pnas.2514698122","DOIUrl":"https://doi.org/10.1073/pnas.2514698122","url":null,"abstract":"Hydrogenases are Nature's sustainable and efficient catalysts for the conversion between H+ and H2. The obstacles that prevented their use as H2 oxidation catalysts in fuel cells are being removed one by one, thanks to the continuous discovery of hydrogenases that have unexpected catalytic properties, the development of new methods for their scalable production and matrices that protect them. Obtaining an efficient biohybrid electrode that is scalable and robust under a large range of experimental conditions is still challenging. The FeFe hydrogenase of Clostridium beijerinckii is a very active catalyst of H2 evolution and can be handled under O2, and its production can potentially be scaled up. However, it was believed that it cannot be used for H2 oxidation, as it is easily oxidized to an O2-stable but inactive state. Here, we show that when the enzyme is embedded into a redox-active film whose reduction potential is finely tuned to the equilibrium potential of the H+/H2 couple, the potential that the enzyme experiences can be buffered in a sharp window that is actually compatible with enzyme-catalyzed H2 oxidation and prevents anaerobic inactivation. This leads us to provide the demonstration of an FeFe hydrogenase-based system that can be used for H2 oxidation and that can be repeatedly exposed to O2 during and between operational cycles.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"128 1","pages":"e2514698122"},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A multilayered gap junction network is essential for social decision-making. 多层次的缝隙连接网络是社会决策的基础。
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-08 DOI: 10.1073/pnas.2510579122
Airi Nakayama,Hiroo Kuroyanagi,Hironori J Matsuyama,Ikue Mori,Naoki Hisamoto,Shunji Nakano
{"title":"A multilayered gap junction network is essential for social decision-making.","authors":"Airi Nakayama,Hiroo Kuroyanagi,Hironori J Matsuyama,Ikue Mori,Naoki Hisamoto,Shunji Nakano","doi":"10.1073/pnas.2510579122","DOIUrl":"https://doi.org/10.1073/pnas.2510579122","url":null,"abstract":"Early-life social experiences can shape adult behavior, yet the underlying neural mechanisms of this plasticity remain incompletely understood. Here, we show that Caenorhabditis elegans larvae reared at high density develop into adults that exhibit exploratory behavior in the associative-learning paradigm known as thermotaxis. While animals grown at low density prefer the temperature previously associated with food, those exposed to high density during larval stages instead disperse from this temperature. The high-density experience alters the neural representation of thermal valence, a process that requires a gap junction network spanning multiple neural circuit layers. This network connects density-sensing neurons to the circuit that processes temperature information. Furthermore, these gap junction components also control the decision to enter developmental diapause in response to high density. Our results suggest that the multilayered gap junction network enables early social experience to influence adult behavior and is essential for developmental and behavioral plasticity in social contexts.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"36 1","pages":"e2510579122"},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction for Kolomenskiy et al., Scaling and mechanical optimality of bristled wings in microinsects. 对Kolomenskiy等人的修正,微生物刚毛翅的尺度和力学最优性。
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-08 DOI: 10.1073/pnas.2526142122
{"title":"Correction for Kolomenskiy et al., Scaling and mechanical optimality of bristled wings in microinsects.","authors":"","doi":"10.1073/pnas.2526142122","DOIUrl":"https://doi.org/10.1073/pnas.2526142122","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"15 1","pages":"e2526142122"},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional genetic elements of a butterfly mimicry supergene. 蝴蝶拟态超基因的功能遗传要素。
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-08 DOI: 10.1073/pnas.2509864122
Nicholas W VanKuren,Sofia I Sheikh,Claire L Fu,Darli Massardo,Namiko N Service,Wei Lu,Marcus R Kronforst
{"title":"Functional genetic elements of a butterfly mimicry supergene.","authors":"Nicholas W VanKuren,Sofia I Sheikh,Claire L Fu,Darli Massardo,Namiko N Service,Wei Lu,Marcus R Kronforst","doi":"10.1073/pnas.2509864122","DOIUrl":"https://doi.org/10.1073/pnas.2509864122","url":null,"abstract":"Development requires the coordinated action of many genes across space and time, yet numerous species can develop discrete, alternate phenotypes. Such complex balanced polymorphisms are often controlled by supergenes: multiple tightly linked loci that function together to control development of a complex phenotype. Supergenes are widespread in nature. However, the evolution and functions of supergene alleles remain obscure because the identities of the functional loci, and the causative variation between them, remain essentially unknown. The doublesex supergene controls mimicry polymorphism in the swallowtail butterflies Papilio polytes and Papilio alphenor. Alternate alleles cause development of discrete mimetic or nonmimetic wing patterns. We found that the mimetic allele evolved by gaining six new cis-regulatory elements (CREs) and an inversion that locked those CREs together with dsx and the novel noncoding gene U3X. At least four of these new CREs are essential for dsx expression and mimetic pattern development. Genome-wide assays of DSX binding suggest that dsx controls mimetic pattern development by directly regulating the expression of both itself and a handful of unlinked genes. The dsx supergene thus contains multiple functional genetic elements, each required for the phenotype switch and linked together by an inversion, and likely exerts its effects on color pattern development through direct regulation of unlinked \"modifier\" genes. Our results therefore support classic theories of supergene evolution, but update those ideas to match what we have learned about gene regulation since their development over a half century ago.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"1 1","pages":"e2509864122"},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Disulfide cross-linked redox-sensitive peptide condensates are efficient cell delivery vehicles of molecular cargo 二硫交联氧化还原敏感肽凝聚物是高效的分子货物细胞递送载体
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-08 DOI: 10.1073/pnas.2515427122
Malay Mondal, Windfield S. Swetman, Shazeed-Ul Karim, Sabin Shrestha, Ashe M. Davis, Fengwei Bai, Faqing Huang, Tristan D. Clemons, Vijayaraghavan Rangachari
{"title":"Disulfide cross-linked redox-sensitive peptide condensates are efficient cell delivery vehicles of molecular cargo","authors":"Malay Mondal, Windfield S. Swetman, Shazeed-Ul Karim, Sabin Shrestha, Ashe M. Davis, Fengwei Bai, Faqing Huang, Tristan D. Clemons, Vijayaraghavan Rangachari","doi":"10.1073/pnas.2515427122","DOIUrl":"https://doi.org/10.1073/pnas.2515427122","url":null,"abstract":"Biomolecular condensates (BCs) are phase-separated viscoelastic hubs within demixed solutions enriched in proteins and nucleic acids. Such condensates, also called membraneless organelles, are increasingly observed in cells and serve as transient hubs for spatial organization and compartmentalization of biomolecules. Along with the transiency of formation and dissolution, their ability to sequester molecules has inspired us to develop BCs as potential vehicles to transport and deliver molecular cargo. We recently reported the design of disulfide bond cross-linked phase-separating peptide (PSP) condensates that spontaneously dissolve in reducing conditions. Based on the premise that the highly reducing cytoplasm could dissolve PSP condensates and release partitioned cargo, here, we demonstrate the ability of PSP condensates to deliver molecular cargo to the cytoplasm of HeLa cells. We show that PSP condensates deliver a variety of cargos that differ in their sizes and chemistries, including small molecules, peptides, GFP (31 kDa), DNA (1.7 kbp), and mRNA. The transfection efficiencies of PSP condensates for delivering DNA and mRNA were also significantly greater than those of a commercial transfection agent. With room to tailor the condensate properties based on cargo and cell types, these results showcase the potential of disulfide-cross-linked PSPs as effective and customizable cellular delivery vehicles, filling a critical demand gap for such delivery systems.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"4 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endosome transcriptomics reveal trafficking of Cajal bodies into multivesicular bodies 内核体转录组学揭示了Cajal小体向多泡小体的转运
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-10-08 DOI: 10.1073/pnas.2511840122
Jasleen Singh, Justin Krish Williams, Quinn Elliott, Rohit Jhawar, Lucas Ferguson, Kathleen Collins, Randy Schekman
{"title":"Endosome transcriptomics reveal trafficking of Cajal bodies into multivesicular bodies","authors":"Jasleen Singh, Justin Krish Williams, Quinn Elliott, Rohit Jhawar, Lucas Ferguson, Kathleen Collins, Randy Schekman","doi":"10.1073/pnas.2511840122","DOIUrl":"https://doi.org/10.1073/pnas.2511840122","url":null,"abstract":"All eukaryotic cells secrete exosomes, a type of extracellular vesicles derived from the endocytic compartments known as multivesicular bodies (MVBs), or late endosomes (LEs). Exosomes contain a diverse range of cargo such as nucleic acids, proteins, lipids, and small molecules but whether these contents have a biological function remains an area of intense investigation. Over the last decade, numerous studies have described the transcriptome of exosomes but very little is known about the RNA content of the MVBs, the source compartment for exosome biogenesis. Here, we determine the small-RNA transcriptome of highly purified MVBs and report that various classes of nuclear small regulatory RNAs such as small-Cajal body associated RNAs, small-nucleolar RNAs, and small-nuclear RNAs traffic to MVBs. We show that this RNA-trafficking requires the function of endosomal sorting complexes required for transport (ESCRT) machinery but is independent of canonical LC3 lipidation mediated selective autophagy. Furthermore, blocking the activity of a PI3K Class 3 enzyme, VPS34, required for recruitment of the ESCRT machinery to the endosome, prevents the turnover of these nuclear RNAs in MVBs. Our results provide a mechanism for targeting nuclear ribonucleoprotein complexes, such as Cajal bodies, for degradation and turnover by the cytoplasmic endo-lysosomal pathway.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"60 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","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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