Pub Date : 2025-11-26DOI: 10.1038/s41580-025-00909-1
M. Burigotto, J. G. Carlton
{"title":"ESCRT-III function in membrane fission and repair","authors":"M. Burigotto, J. G. Carlton","doi":"10.1038/s41580-025-00909-1","DOIUrl":"https://doi.org/10.1038/s41580-025-00909-1","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"3 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.1038/s41580-025-00897-2
Christopher Chin Sang,Sayantani Upadhyay,Michael L Nosella,Julie D Forman-Kay,Hyun O Lee
Biomolecular condensates are non-membrane-encapsulated compartments that control various biological processes, largely by enriching and excluding certain molecules. Emerging evidence demonstrates that condensate compositions dynamically change in response to stimuli and over time. Thus, condensates that share a designation and general function can substantially vary in their composition. In this Review, we discuss the current understanding of condensate composition changes and heterogeneity, how they are regulated and how the changes affect biochemical reactions. We focus on four condensates: DNA double-strand break (DSB) repair foci, promyelocytic leukaemia (PML) nuclear bodies, processing bodies (P-bodies) and RNA transport granules, with examples from stress granules and germ granules. Changes in condensate composition seem to support complex reactions, such as those occurring in DNA repair and RNA processing. Mechanisms regulating composition changes include biophysical features of components, modifications, nodes and enzymatic reactions. We also speculate about the impact of protein mislocalization and mutations on condensate composition and function, including in cancer and neurodegenerative diseases. We conclude by discussing outstanding questions and the implications of studying condensate composition changes for research and therapeutics.
{"title":"The dynamic and heterogeneous composition of biomolecular condensates and its functional relevance.","authors":"Christopher Chin Sang,Sayantani Upadhyay,Michael L Nosella,Julie D Forman-Kay,Hyun O Lee","doi":"10.1038/s41580-025-00897-2","DOIUrl":"https://doi.org/10.1038/s41580-025-00897-2","url":null,"abstract":"Biomolecular condensates are non-membrane-encapsulated compartments that control various biological processes, largely by enriching and excluding certain molecules. Emerging evidence demonstrates that condensate compositions dynamically change in response to stimuli and over time. Thus, condensates that share a designation and general function can substantially vary in their composition. In this Review, we discuss the current understanding of condensate composition changes and heterogeneity, how they are regulated and how the changes affect biochemical reactions. We focus on four condensates: DNA double-strand break (DSB) repair foci, promyelocytic leukaemia (PML) nuclear bodies, processing bodies (P-bodies) and RNA transport granules, with examples from stress granules and germ granules. Changes in condensate composition seem to support complex reactions, such as those occurring in DNA repair and RNA processing. Mechanisms regulating composition changes include biophysical features of components, modifications, nodes and enzymatic reactions. We also speculate about the impact of protein mislocalization and mutations on condensate composition and function, including in cancer and neurodegenerative diseases. We conclude by discussing outstanding questions and the implications of studying condensate composition changes for research and therapeutics.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"30 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1038/s41580-025-00915-3
Marjolein van Sluis, Camila Gonzalo-Hansen, Qingrong Li, Hannes Lans, Dong Wang, Jurgen A. Marteijn
RNA polymerase II (Pol II)-mediated gene transcription is frequently disrupted by DNA damage from various sources. Transcription-blocking DNA lesions hinder the progression of elongating Pol II, leading to transcription stress that, if unresolved, causes cellular dysfunction, neurodegeneration and ageing. In this Review, we discuss how different types of lesion are recognized by obstructing Pol II and removed by the intricate transcription-coupled nucleotide excision repair (TC-NER) pathway, emphasizing recent structural findings that reveal key aspects of the TC-NER mechanism. We also discuss the mechanisms proposed for processing lesion-stalled Pol II, which is crucial to facilitate TC-NER, and focus on how Pol II ubiquitylation orchestrates repair-complex assembly and Pol II degradation. In addition, we discuss the alternative mechanism of transcription-coupled DNA–protein crosslink repair, which was recently identified to be important for resolving DNA–protein crosslinks in active genes. Finally, we describe how these insights elucidate the different pathological causes of hereditary TC-NER deficiencies, namely of the mild cutaneous ultraviolet-sensitive syndrome and the severe progeroid Cockayne syndrome. Transcription-blocking DNA lesions lead to transcription stress that is associated with neurodegeneration and accelerated ageing. Recent structural and other findings have clarified how different obstructing lesions are recognized and removed and shed new light on the causes of various pathologies of repair deficiencies.
{"title":"Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease","authors":"Marjolein van Sluis, Camila Gonzalo-Hansen, Qingrong Li, Hannes Lans, Dong Wang, Jurgen A. Marteijn","doi":"10.1038/s41580-025-00915-3","DOIUrl":"10.1038/s41580-025-00915-3","url":null,"abstract":"RNA polymerase II (Pol II)-mediated gene transcription is frequently disrupted by DNA damage from various sources. Transcription-blocking DNA lesions hinder the progression of elongating Pol II, leading to transcription stress that, if unresolved, causes cellular dysfunction, neurodegeneration and ageing. In this Review, we discuss how different types of lesion are recognized by obstructing Pol II and removed by the intricate transcription-coupled nucleotide excision repair (TC-NER) pathway, emphasizing recent structural findings that reveal key aspects of the TC-NER mechanism. We also discuss the mechanisms proposed for processing lesion-stalled Pol II, which is crucial to facilitate TC-NER, and focus on how Pol II ubiquitylation orchestrates repair-complex assembly and Pol II degradation. In addition, we discuss the alternative mechanism of transcription-coupled DNA–protein crosslink repair, which was recently identified to be important for resolving DNA–protein crosslinks in active genes. Finally, we describe how these insights elucidate the different pathological causes of hereditary TC-NER deficiencies, namely of the mild cutaneous ultraviolet-sensitive syndrome and the severe progeroid Cockayne syndrome. Transcription-blocking DNA lesions lead to transcription stress that is associated with neurodegeneration and accelerated ageing. Recent structural and other findings have clarified how different obstructing lesions are recognized and removed and shed new light on the causes of various pathologies of repair deficiencies.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"27 3","pages":"234-251"},"PeriodicalIF":90.2,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1038/s41580-025-00931-3
Lang Ding
In this Tools of the Trade article, Ding (Wang lab) describes the development of tissue expansion-enhanced mass-spectrometry imaging (TEMI), which combines an optimized tissue expansion method with mass spectrometry imaging to obtain multi-omic data at high spatial resolution and is compatible with expansion microscopy.
{"title":"Tissue expansion-enhanced mass-spectrometry imaging decodes biomolecular landscapes","authors":"Lang Ding","doi":"10.1038/s41580-025-00931-3","DOIUrl":"10.1038/s41580-025-00931-3","url":null,"abstract":"In this Tools of the Trade article, Ding (Wang lab) describes the development of tissue expansion-enhanced mass-spectrometry imaging (TEMI), which combines an optimized tissue expansion method with mass spectrometry imaging to obtain multi-omic data at high spatial resolution and is compatible with expansion microscopy.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"27 3","pages":"173-173"},"PeriodicalIF":90.2,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1038/s41580-025-00928-y
Timo N. Kohler
Timo Kohler highlights a study in which in vitro fertilization and cell culture techniques were adapted to generate chimeric blastocysts from northern and southern white rhinoceros species and establish embryonic stem cell lines — which has important implications for the conservation of endangered species and biodiversity.
Timo Kohler重点介绍了一项研究，该研究采用体外受精和细胞培养技术，从北方和南方白犀牛物种中产生嵌合囊胚，并建立胚胎干细胞系，这对保护濒危物种和生物多样性具有重要意义。
{"title":"From pluripotency to species conservation","authors":"Timo N. Kohler","doi":"10.1038/s41580-025-00928-y","DOIUrl":"10.1038/s41580-025-00928-y","url":null,"abstract":"Timo Kohler highlights a study in which in vitro fertilization and cell culture techniques were adapted to generate chimeric blastocysts from northern and southern white rhinoceros species and establish embryonic stem cell lines — which has important implications for the conservation of endangered species and biodiversity.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"27 3","pages":"176-176"},"PeriodicalIF":90.2,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1038/s41580-025-00930-4
Mengxi Zhang
In this Tools of the Trade article, Zhang (Xiao Lab) highlights the development of a rotor-based fluorescent amino acid that acts as a sensor for crowded protein microenvironments, enabling researchers to monitor protein behaviour in vivo.
{"title":"Illuminating protein microenvironments with rotor-based fluorescent amino acids","authors":"Mengxi Zhang","doi":"10.1038/s41580-025-00930-4","DOIUrl":"10.1038/s41580-025-00930-4","url":null,"abstract":"In this Tools of the Trade article, Zhang (Xiao Lab) highlights the development of a rotor-based fluorescent amino acid that acts as a sensor for crowded protein microenvironments, enabling researchers to monitor protein behaviour in vivo.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"27 2","pages":"92-92"},"PeriodicalIF":90.2,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1038/s41580-025-00917-1
Sushant Bangru,Rocky Diegmiller,Stefano Di Talia,Kenneth D Poss
Tissue regeneration has historically been the subject of intense scientific scrutiny, from basic biology to applications in regenerative medicine. Use of model organisms and cutting-edge technologies have uncovered various mechanisms of regeneration, but understanding how signals are regulated spatiotemporally to renew lost structures at scale remains a challenge. Recent insights into chromatin structure and enhancer regulation, immune-tissue crosstalk, bioelectric and metabolic cues and quantitative modelling are broadening and reshaping our understanding of how tissues repair and renew. The evolution of cutting-edge tools for in vivo profiling and tracking of single cells is providing unprecedented dynamic views of regeneration across scales. Here, we synthesize the current knowledge of signal control in regeneration, with emphasis on conceptual advances, technical innovations and future directions for a more quantitative understanding of regenerative biology.
{"title":"Signal control during tissue regeneration in adult animals.","authors":"Sushant Bangru,Rocky Diegmiller,Stefano Di Talia,Kenneth D Poss","doi":"10.1038/s41580-025-00917-1","DOIUrl":"https://doi.org/10.1038/s41580-025-00917-1","url":null,"abstract":"Tissue regeneration has historically been the subject of intense scientific scrutiny, from basic biology to applications in regenerative medicine. Use of model organisms and cutting-edge technologies have uncovered various mechanisms of regeneration, but understanding how signals are regulated spatiotemporally to renew lost structures at scale remains a challenge. Recent insights into chromatin structure and enhancer regulation, immune-tissue crosstalk, bioelectric and metabolic cues and quantitative modelling are broadening and reshaping our understanding of how tissues repair and renew. The evolution of cutting-edge tools for in vivo profiling and tracking of single cells is providing unprecedented dynamic views of regeneration across scales. Here, we synthesize the current knowledge of signal control in regeneration, with emphasis on conceptual advances, technical innovations and future directions for a more quantitative understanding of regenerative biology.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"54 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1038/s41580-025-00907-3
Emma T. Watson, William R. Wegeng, Stamatina Aravani, Andreas M. Ernst, Julia von Blume
The Golgi apparatus has a central role in the formation and trafficking of glycoproteins and lipids. It is organized into a series of flattened, membrane-bound compartments called cisternae, each housing a unique set of resident proteins that sequentially modify newly synthesized proteins and lipids as they move through the Golgi stack. In the final compartments, known as the trans-Golgi network (TGN), the processed cargoes are sorted and packaged into transport carriers. Despite substantial progress, key questions remain about how proteins and lipids are selectively sorted within the Golgi for delivery to specific destinations. In this Review we highlight recent insights on the biogenesis of membrane carriers at the TGN that enable transport of macromolecules along the secretory pathway and discuss how dysfunction of the molecular machinery gives rise to Golgi-related diseases. Protein and lipid cargoes are modified and sorted in the Golgi apparatus and packaged for delivery to diverse cellular destinations at the trans-Golgi network (TGN). This Review discusses recent insights into Golgi transport mechanisms and carrier biogenesis at the TGN.
{"title":"Mechanistic insights into cargo sorting and export from the Golgi apparatus","authors":"Emma T. Watson, William R. Wegeng, Stamatina Aravani, Andreas M. Ernst, Julia von Blume","doi":"10.1038/s41580-025-00907-3","DOIUrl":"10.1038/s41580-025-00907-3","url":null,"abstract":"The Golgi apparatus has a central role in the formation and trafficking of glycoproteins and lipids. It is organized into a series of flattened, membrane-bound compartments called cisternae, each housing a unique set of resident proteins that sequentially modify newly synthesized proteins and lipids as they move through the Golgi stack. In the final compartments, known as the trans-Golgi network (TGN), the processed cargoes are sorted and packaged into transport carriers. Despite substantial progress, key questions remain about how proteins and lipids are selectively sorted within the Golgi for delivery to specific destinations. In this Review we highlight recent insights on the biogenesis of membrane carriers at the TGN that enable transport of macromolecules along the secretory pathway and discuss how dysfunction of the molecular machinery gives rise to Golgi-related diseases. Protein and lipid cargoes are modified and sorted in the Golgi apparatus and packaged for delivery to diverse cellular destinations at the trans-Golgi network (TGN). This Review discusses recent insights into Golgi transport mechanisms and carrier biogenesis at the TGN.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 12","pages":"940-956"},"PeriodicalIF":90.2,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145478132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1038/s41580-025-00914-4
Weili Miao, Douglas F. Porter, Vanessa Lopez-Pajares, Paul A. Khavari
RNA-binding proteins (RBPs) are essential for post-transcriptional gene regulation, including for RNA modification such as N6-methyladenosine (m6A), splicing, polyadenylation, localization, translation and decay. Dysregulation of RBPs has been causally linked to a wide array of human diseases, including cancer, neurodegenerative diseases, metabolic disorders and tissue differentiation abnormalities. Although RBPs have traditionally been studied through their RNA, protein and post-translational interactions, growing evidence shows that small biomolecules (SBMs) such as sugars, nucleotides, metabolites such as S-adenosylmethionine (SAM) and NAD(P)H, and drugs can directly bind RBPs and modulate their structure, localization and RNA-binding activity. These context-dependent and concentration-dependent interactions link RBP regulation to cellular metabolism and are a key focus of current research. In this Review, we discuss the expanding landscape of SBM-binding RBPs and the functions of these RBPs in condensate formation, RNA localization, processing and translation. We highlight the molecular principles that underlie these interactions and their functional relevance to human diseases. We also examine recent advances in the identification of SBM–RBP interactions and the innovative methodologies that are driving discoveries in this rapidly advancing field. Together, these insights underscore the potential of SBMs to modulate RBPs and inform novel therapeutic strategies. RNA-binding proteins (RBPs) are essential for gene regulation. Recent data reveal that small biomolecules (SBMs) such as sugars, nucleotides, metabolites and drugs bind to RBPs and regulate their function. This Review discusses the landscape of SBM-binding RBPs, the molecular basis of their interactions and their relevance to human diseases.
{"title":"Regulation of RNA-binding proteins by small biomolecules","authors":"Weili Miao, Douglas F. Porter, Vanessa Lopez-Pajares, Paul A. Khavari","doi":"10.1038/s41580-025-00914-4","DOIUrl":"10.1038/s41580-025-00914-4","url":null,"abstract":"RNA-binding proteins (RBPs) are essential for post-transcriptional gene regulation, including for RNA modification such as N6-methyladenosine (m6A), splicing, polyadenylation, localization, translation and decay. Dysregulation of RBPs has been causally linked to a wide array of human diseases, including cancer, neurodegenerative diseases, metabolic disorders and tissue differentiation abnormalities. Although RBPs have traditionally been studied through their RNA, protein and post-translational interactions, growing evidence shows that small biomolecules (SBMs) such as sugars, nucleotides, metabolites such as S-adenosylmethionine (SAM) and NAD(P)H, and drugs can directly bind RBPs and modulate their structure, localization and RNA-binding activity. These context-dependent and concentration-dependent interactions link RBP regulation to cellular metabolism and are a key focus of current research. In this Review, we discuss the expanding landscape of SBM-binding RBPs and the functions of these RBPs in condensate formation, RNA localization, processing and translation. We highlight the molecular principles that underlie these interactions and their functional relevance to human diseases. We also examine recent advances in the identification of SBM–RBP interactions and the innovative methodologies that are driving discoveries in this rapidly advancing field. Together, these insights underscore the potential of SBMs to modulate RBPs and inform novel therapeutic strategies. RNA-binding proteins (RBPs) are essential for gene regulation. Recent data reveal that small biomolecules (SBMs) such as sugars, nucleotides, metabolites and drugs bind to RBPs and regulate their function. This Review discusses the landscape of SBM-binding RBPs, the molecular basis of their interactions and their relevance to human diseases.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"27 3","pages":"213-233"},"PeriodicalIF":90.2,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1038/s41580-025-00927-z
Barbara Demmig-Adams
{"title":"First molecular evidence for zeaxanthin’s role in energy dissipation","authors":"Barbara Demmig-Adams","doi":"10.1038/s41580-025-00927-z","DOIUrl":"https://doi.org/10.1038/s41580-025-00927-z","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"1 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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