Pub Date : 2024-04-05DOI: 10.1038/s41580-024-00731-1
Tineke L. Lenstra
Imaging of fluorescently labelled nascent RNA in live cells enabled real-time observation of transcription of an endogenous gene.
通过对活细胞中荧光标记的新生 RNA 进行成像，可以实时观察内源基因的转录情况。
{"title":"Seeing transcription in real time","authors":"Tineke L. Lenstra","doi":"10.1038/s41580-024-00731-1","DOIUrl":"10.1038/s41580-024-00731-1","url":null,"abstract":"Imaging of fluorescently labelled nascent RNA in live cells enabled real-time observation of transcription of an endogenous gene.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140349579","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 : 2024-04-02DOI: 10.1038/s41580-024-00718-y
Dina Listov, Casper A. Goverde, Bruno E. Correia, Sarel Jacob Fleishman
The field of protein design has made remarkable progress over the past decade. Historically, the low reliability of purely structure-based design methods limited their application, but recent strategies that combine structure-based and sequence-based calculations, as well as machine learning tools, have dramatically improved protein engineering and design. In this Review, we discuss how these methods have enabled the design of increasingly complex structures and therapeutically relevant activities. Additionally, protein optimization methods have improved the stability and activity of complex eukaryotic proteins. Thanks to their increased reliability, computational design methods have been applied to improve therapeutics and enzymes for green chemistry and have generated vaccine antigens, antivirals and drug-delivery nano-vehicles. Moreover, the high success of design methods reflects an increased understanding of basic rules that govern the relationships among protein sequence, structure and function. However, de novo design is still limited mostly to α-helix bundles, restricting its potential to generate sophisticated enzymes and diverse protein and small-molecule binders. Designing complex protein structures is a challenging but necessary next step if we are to realize our objective of generating new-to-nature activities. Recent combinations of structure-based and sequence-based calculations and machine learning tools have dramatically improved protein engineering and design. Although designing complex protein structures remains challenging, these methods have enabled the design of therapeutically relevant activities, including vaccine antigens, antivirals and drug-delivery nano-vehicles.
{"title":"Opportunities and challenges in design and optimization of protein function","authors":"Dina Listov, Casper A. Goverde, Bruno E. Correia, Sarel Jacob Fleishman","doi":"10.1038/s41580-024-00718-y","DOIUrl":"10.1038/s41580-024-00718-y","url":null,"abstract":"The field of protein design has made remarkable progress over the past decade. Historically, the low reliability of purely structure-based design methods limited their application, but recent strategies that combine structure-based and sequence-based calculations, as well as machine learning tools, have dramatically improved protein engineering and design. In this Review, we discuss how these methods have enabled the design of increasingly complex structures and therapeutically relevant activities. Additionally, protein optimization methods have improved the stability and activity of complex eukaryotic proteins. Thanks to their increased reliability, computational design methods have been applied to improve therapeutics and enzymes for green chemistry and have generated vaccine antigens, antivirals and drug-delivery nano-vehicles. Moreover, the high success of design methods reflects an increased understanding of basic rules that govern the relationships among protein sequence, structure and function. However, de novo design is still limited mostly to α-helix bundles, restricting its potential to generate sophisticated enzymes and diverse protein and small-molecule binders. Designing complex protein structures is a challenging but necessary next step if we are to realize our objective of generating new-to-nature activities. Recent combinations of structure-based and sequence-based calculations and machine learning tools have dramatically improved protein engineering and design. Although designing complex protein structures remains challenging, these methods have enabled the design of therapeutically relevant activities, including vaccine antigens, antivirals and drug-delivery nano-vehicles.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":81.3,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140346359","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 : 2024-03-28DOI: 10.1038/s41580-024-00726-y
Marc R. Friedländer, M. Thomas P. Gilbert
Although normally transient, RNA can persist postmortem when preserved by cold, desiccation or chemical treatment. In this Comment, we discuss how ancient RNA enables the study of gene expression of (pre)historic viruses, plants and animals going back at least as far as the last Ice Age. Friedländer and Gilbert introduce the study of ancient RNA of viruses, plants and animals, and how it can inform us of (pre)historic gene expression.
{"title":"How ancient RNA survives and what we can learn from it","authors":"Marc R. Friedländer, M. Thomas P. Gilbert","doi":"10.1038/s41580-024-00726-y","DOIUrl":"10.1038/s41580-024-00726-y","url":null,"abstract":"Although normally transient, RNA can persist postmortem when preserved by cold, desiccation or chemical treatment. In this Comment, we discuss how ancient RNA enables the study of gene expression of (pre)historic viruses, plants and animals going back at least as far as the last Ice Age. Friedländer and Gilbert introduce the study of ancient RNA of viruses, plants and animals, and how it can inform us of (pre)historic gene expression.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318796","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 : 2024-03-25DOI: 10.1038/s41580-024-00722-2
Larisa Venkova, Henri Popard
In this Tools of the Trade article, Venkova and Popard (Piel lab) discuss recent updates to the fluorescence exclusion method that now enable simultaneous measurement of cellular and nuclear size as well as investigation of small prokaryotic cells.
{"title":"Single-cell live volume measurements using the fluorescence exclusion method","authors":"Larisa Venkova, Henri Popard","doi":"10.1038/s41580-024-00722-2","DOIUrl":"10.1038/s41580-024-00722-2","url":null,"abstract":"In this Tools of the Trade article, Venkova and Popard (Piel lab) discuss recent updates to the fluorescence exclusion method that now enable simultaneous measurement of cellular and nuclear size as well as investigation of small prokaryotic cells.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140209839","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 : 2024-03-25DOI: 10.1038/s41580-024-00715-1
Oscar A. Peña, Paul Martin
Wound healing is a complex process that involves the coordinated actions of many different tissues and cell lineages. It requires tight orchestration of cell migration, proliferation, matrix deposition and remodelling, alongside inflammation and angiogenesis. Whereas small skin wounds heal in days, larger injuries resulting from trauma, acute illness or major surgery can take several weeks to heal, generally leaving behind a fibrotic scar that can impact tissue function. Development of therapeutics to prevent scarring and successfully repair chronic wounds requires a fuller knowledge of the cellular and molecular mechanisms driving wound healing. In this Review, we discuss the current understanding of the different phases of wound healing, from clot formation through re-epithelialization, angiogenesis and subsequent scar deposition. We highlight the contribution of different cell types to skin repair, with emphasis on how both innate and adaptive immune cells in the wound inflammatory response influence classically studied wound cell lineages, including keratinocytes, fibroblasts and endothelial cells, but also some of the less-studied cell lineages such as adipocytes, melanocytes and cutaneous nerves. Finally, we discuss newer approaches and research directions that have the potential to further our understanding of the mechanisms underpinning tissue repair. This Review discusses the complex mechanisms of wound healing — cell migration, matrix remodelling, inflammation and angiogenesis — and the contributions of different cell types, including immune cells, to this process. It also highlights new methodologies that could inform future therapies to prevent scarring and repair chronic wounds.
{"title":"Cellular and molecular mechanisms of skin wound healing","authors":"Oscar A. Peña, Paul Martin","doi":"10.1038/s41580-024-00715-1","DOIUrl":"10.1038/s41580-024-00715-1","url":null,"abstract":"Wound healing is a complex process that involves the coordinated actions of many different tissues and cell lineages. It requires tight orchestration of cell migration, proliferation, matrix deposition and remodelling, alongside inflammation and angiogenesis. Whereas small skin wounds heal in days, larger injuries resulting from trauma, acute illness or major surgery can take several weeks to heal, generally leaving behind a fibrotic scar that can impact tissue function. Development of therapeutics to prevent scarring and successfully repair chronic wounds requires a fuller knowledge of the cellular and molecular mechanisms driving wound healing. In this Review, we discuss the current understanding of the different phases of wound healing, from clot formation through re-epithelialization, angiogenesis and subsequent scar deposition. We highlight the contribution of different cell types to skin repair, with emphasis on how both innate and adaptive immune cells in the wound inflammatory response influence classically studied wound cell lineages, including keratinocytes, fibroblasts and endothelial cells, but also some of the less-studied cell lineages such as adipocytes, melanocytes and cutaneous nerves. Finally, we discuss newer approaches and research directions that have the potential to further our understanding of the mechanisms underpinning tissue repair. This Review discusses the complex mechanisms of wound healing — cell migration, matrix remodelling, inflammation and angiogenesis — and the contributions of different cell types, including immune cells, to this process. It also highlights new methodologies that could inform future therapies to prevent scarring and repair chronic wounds.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":81.3,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140209767","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 : 2024-03-22DOI: 10.1038/s41580-024-00723-1
Thomas Arnesen, Ine Kjosås, Nina McTiernan
Despite being one of the most common protein modifications in eukaryotes, the cellular effect of N-terminal acetylation remains cryptic. Four decades ago, the nature of the N terminus was linked to protein stability. In this Comment, we discuss an emerging major role of N-terminal acetylation in shielding the proteome from degradation. Thomas Arnesen and colleagues discuss an emerging major role of one of the most common protein modifications, N-terminal acetylation, in shielding the proteome from degradation.
尽管N-末端乙酰化是真核生物中最常见的蛋白质修饰之一，但它对细胞的影响仍然是未知的。40 年前，N 端的性质与蛋白质的稳定性有关。在这篇评论中，我们将讨论 N 端乙酰化在保护蛋白质组不被降解方面新出现的重要作用。Thomas Arnesen 及其同事讨论了最常见的蛋白质修饰之一--N-末端乙酰化--在保护蛋白质组不被降解方面新出现的重要作用。
{"title":"Protein N-terminal acetylation is entering the degradation end game","authors":"Thomas Arnesen, Ine Kjosås, Nina McTiernan","doi":"10.1038/s41580-024-00723-1","DOIUrl":"10.1038/s41580-024-00723-1","url":null,"abstract":"Despite being one of the most common protein modifications in eukaryotes, the cellular effect of N-terminal acetylation remains cryptic. Four decades ago, the nature of the N terminus was linked to protein stability. In this Comment, we discuss an emerging major role of N-terminal acetylation in shielding the proteome from degradation. Thomas Arnesen and colleagues discuss an emerging major role of one of the most common protein modifications, N-terminal acetylation, in shielding the proteome from degradation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140192676","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 : 2024-03-21DOI: 10.1038/s41580-024-00725-z
Ahna Skop, Karen Schindler
Ahna Skop and Karen Schindler describe a paper that found localized translation in mammalian embryos, demonstrating the importance of RNA transport for development.
{"title":"Localized translation in the embryo","authors":"Ahna Skop, Karen Schindler","doi":"10.1038/s41580-024-00725-z","DOIUrl":"10.1038/s41580-024-00725-z","url":null,"abstract":"Ahna Skop and Karen Schindler describe a paper that found localized translation in mammalian embryos, demonstrating the importance of RNA transport for development.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140182936","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 : 2024-03-21DOI: 10.1038/s41580-024-00724-0
Susanne Bornelöv
The story of a paper that established the concept of codon optimality and its connection with translation efficiency and mRNA decay.
一篇论文的故事，这篇论文确立了密码子最优性的概念及其与翻译效率和 mRNA 衰减之间的联系。
{"title":"A code within the genetic code","authors":"Susanne Bornelöv","doi":"10.1038/s41580-024-00724-0","DOIUrl":"10.1038/s41580-024-00724-0","url":null,"abstract":"The story of a paper that established the concept of codon optimality and its connection with translation efficiency and mRNA decay.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140182872","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 : 2024-03-20DOI: 10.1038/s41580-024-00706-2
Morgan Shine, Jackson Gordon, Leonard Schärfen, Dagmar Zigackova, Lydia Herzel, Karla M. Neugebauer
Many steps of RNA processing occur during transcription by RNA polymerases. Co-transcriptional activities are deemed commonplace in prokaryotes, in which the lack of membrane barriers allows mixing of all gene expression steps, from transcription to translation. In the past decade, an extraordinary level of coordination between transcription and RNA processing has emerged in eukaryotes. In this Review, we discuss recent developments in our understanding of co-transcriptional gene regulation in both eukaryotes and prokaryotes, comparing methodologies and mechanisms, and highlight striking parallels in how RNA polymerases interact with the machineries that act on nascent RNA. The development of RNA sequencing and imaging techniques that detect transient transcription and RNA processing intermediates has facilitated discoveries of transcription coordination with splicing, 3′-end cleavage and dynamic RNA folding and revealed physical contacts between processing machineries and RNA polymerases. Such studies indicate that intron retention in a given nascent transcript can prevent 3′-end cleavage and cause transcriptional readthrough, which is a hallmark of eukaryotic cellular stress responses. We also discuss how coordination between nascent RNA biogenesis and transcription drives fundamental aspects of gene expression in both prokaryotes and eukaryotes. Methodological advances have enabled discoveries of RNA polymerase interactions with RNA processing machineries, such as the splicing and 3′-end cleavage machineries. This Review discusses the roles of these interactions in gene regulation and eukaryotic cellular stress responses, and highlights parallels between co-transcriptional RNA processing in eukaryotes and prokaryotes.
{"title":"Co-transcriptional gene regulation in eukaryotes and prokaryotes","authors":"Morgan Shine, Jackson Gordon, Leonard Schärfen, Dagmar Zigackova, Lydia Herzel, Karla M. Neugebauer","doi":"10.1038/s41580-024-00706-2","DOIUrl":"10.1038/s41580-024-00706-2","url":null,"abstract":"Many steps of RNA processing occur during transcription by RNA polymerases. Co-transcriptional activities are deemed commonplace in prokaryotes, in which the lack of membrane barriers allows mixing of all gene expression steps, from transcription to translation. In the past decade, an extraordinary level of coordination between transcription and RNA processing has emerged in eukaryotes. In this Review, we discuss recent developments in our understanding of co-transcriptional gene regulation in both eukaryotes and prokaryotes, comparing methodologies and mechanisms, and highlight striking parallels in how RNA polymerases interact with the machineries that act on nascent RNA. The development of RNA sequencing and imaging techniques that detect transient transcription and RNA processing intermediates has facilitated discoveries of transcription coordination with splicing, 3′-end cleavage and dynamic RNA folding and revealed physical contacts between processing machineries and RNA polymerases. Such studies indicate that intron retention in a given nascent transcript can prevent 3′-end cleavage and cause transcriptional readthrough, which is a hallmark of eukaryotic cellular stress responses. We also discuss how coordination between nascent RNA biogenesis and transcription drives fundamental aspects of gene expression in both prokaryotes and eukaryotes. Methodological advances have enabled discoveries of RNA polymerase interactions with RNA processing machineries, such as the splicing and 3′-end cleavage machineries. This Review discusses the roles of these interactions in gene regulation and eukaryotic cellular stress responses, and highlights parallels between co-transcriptional RNA processing in eukaryotes and prokaryotes.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":81.3,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175700","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 : 2024-03-13DOI: 10.1038/s41580-024-00721-3
Aleksi Isomursu
In this Tools of the Trade article, Isomursu (Ivaska lab) describes a new method for dynamic micropatterning, which enables investigation of cell adhesion and migration on substrates that mimic different extracellular matrix environments.
在这篇《贸易工具》（Tools of the Trade）文章中，Isomursu（伊瓦斯卡实验室）介绍了一种动态微图案化的新方法，这种方法可以研究细胞在模拟不同细胞外基质环境的基底上的粘附和迁移。
{"title":"Spatiotemporal control over cell–matrix interactions using dynamic micropatterns","authors":"Aleksi Isomursu","doi":"10.1038/s41580-024-00721-3","DOIUrl":"10.1038/s41580-024-00721-3","url":null,"abstract":"In this Tools of the Trade article, Isomursu (Ivaska lab) describes a new method for dynamic micropatterning, which enables investigation of cell adhesion and migration on substrates that mimic different extracellular matrix environments.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120171","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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