Pub Date : 2023-12-11DOI: 10.1038/s41580-023-00693-w
Hub Zwart
The Building a Synthetic Cell (BaSyC) consortium — launched in 2017 — proposes to create “an autonomous self-reproducing cell that can sustain itself, replicate and divide”. I joined this consortium to explore the bioethics of creating synthetic cells, by embedding philosophical reflection into research practices. In this Comment, Hub Zwart discusses the importance of embedding philosophical reflection into research aiming at creating a synthetic cell.
{"title":"The bioethics of synthetic cells","authors":"Hub Zwart","doi":"10.1038/s41580-023-00693-w","DOIUrl":"10.1038/s41580-023-00693-w","url":null,"abstract":"The Building a Synthetic Cell (BaSyC) consortium — launched in 2017 — proposes to create “an autonomous self-reproducing cell that can sustain itself, replicate and divide”. I joined this consortium to explore the bioethics of creating synthetic cells, by embedding philosophical reflection into research practices. In this Comment, Hub Zwart discusses the importance of embedding philosophical reflection into research aiming at creating a synthetic cell.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138564886","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 : 2023-12-05DOI: 10.1038/s41580-023-00624-9
Jailson Brito Querido, Irene Díaz-López, V. Ramakrishnan
The regulation of gene expression is fundamental for life. Whereas the role of transcriptional regulation of gene expression has been studied for several decades, it has been clear over the past two decades that post-transcriptional regulation of gene expression, of which translation regulation is a major part, can be equally important. Translation can be divided into four main stages: initiation, elongation, termination and ribosome recycling. Translation is controlled mainly during its initiation, a process which culminates in a ribosome positioned with an initiator tRNA over the start codon and, thus, ready to begin elongation of the protein chain. mRNA translation has emerged as a powerful tool for the development of innovative therapies, yet the detailed mechanisms underlying the complex process of initiation remain unclear. Recent studies in yeast and mammals have started to shed light on some previously unclear aspects of this process. In this Review, we discuss the current state of knowledge on eukaryotic translation initiation and its regulation in health and disease. Specifically, we focus on recent advances in understanding the processes involved in assembling the 43S pre-initiation complex and its recruitment by the cap-binding complex eukaryotic translation initiation factor 4F (eIF4F) at the 5′ end of mRNA. In addition, we discuss recent insights into ribosome scanning along the 5′ untranslated region of mRNA and selection of the start codon, which culminates in joining of the 60S large subunit and formation of the 80S initiation complex. Translation is controlled mainly during its initiation. Recent studies in yeast and mammals provide new insights into the mechanism of translation initiation regulation in health and in various diseases, and open avenues for the development of innovative therapies targeting the translation machinery.
{"title":"The molecular basis of translation initiation and its regulation in eukaryotes","authors":"Jailson Brito Querido, Irene Díaz-López, V. Ramakrishnan","doi":"10.1038/s41580-023-00624-9","DOIUrl":"10.1038/s41580-023-00624-9","url":null,"abstract":"The regulation of gene expression is fundamental for life. Whereas the role of transcriptional regulation of gene expression has been studied for several decades, it has been clear over the past two decades that post-transcriptional regulation of gene expression, of which translation regulation is a major part, can be equally important. Translation can be divided into four main stages: initiation, elongation, termination and ribosome recycling. Translation is controlled mainly during its initiation, a process which culminates in a ribosome positioned with an initiator tRNA over the start codon and, thus, ready to begin elongation of the protein chain. mRNA translation has emerged as a powerful tool for the development of innovative therapies, yet the detailed mechanisms underlying the complex process of initiation remain unclear. Recent studies in yeast and mammals have started to shed light on some previously unclear aspects of this process. In this Review, we discuss the current state of knowledge on eukaryotic translation initiation and its regulation in health and disease. Specifically, we focus on recent advances in understanding the processes involved in assembling the 43S pre-initiation complex and its recruitment by the cap-binding complex eukaryotic translation initiation factor 4F (eIF4F) at the 5′ end of mRNA. In addition, we discuss recent insights into ribosome scanning along the 5′ untranslated region of mRNA and selection of the start codon, which culminates in joining of the 60S large subunit and formation of the 80S initiation complex. Translation is controlled mainly during its initiation. Recent studies in yeast and mammals provide new insights into the mechanism of translation initiation regulation in health and in various diseases, and open avenues for the development of innovative therapies targeting the translation machinery.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138485365","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 : 2023-11-24DOI: 10.1038/s41580-023-00676-x
Carmine Settembre, Rushika M. Perera
Every cell must satisfy basic requirements for nutrient sensing, utilization and recycling through macromolecular breakdown to coordinate programmes for growth, repair and stress adaptation. The lysosome orchestrates these key functions through the synchronised interplay between hydrolytic enzymes, nutrient transporters and signalling factors, which together enable metabolic coordination with other organelles and regulation of specific gene expression programmes. In this Review, we discuss recent findings on lysosome-dependent signalling pathways, focusing on how the lysosome senses nutrient availability through its physical and functional association with mechanistic target of rapamycin complex 1 (mTORC1) and how, in response, the microphthalmia/transcription factor E (MiT/TFE) transcription factors exert feedback regulation on lysosome biogenesis. We also highlight the emerging interactions of lysosomes with other organelles, which contribute to cellular homeostasis. Lastly, we discuss how lysosome dysfunction contributes to diverse disease pathologies and how inherited mutations that compromise lysosomal hydrolysis, transport or signalling components lead to multi-organ disorders with severe metabolic and neurological impact. A deeper comprehension of lysosomal composition and function, at both the cellular and organismal level, may uncover fundamental insights into human physiology and disease. Lysosomes orchestrate key cellular functions such as nutrient sensing, degradation of macromolecules and stress adaptation. This Review discusses the integration of signalling pathways at the lysosome and highlights the interaction of lysosomes with other organelles and mechanisms that ensure lysosome homeostasis.
{"title":"Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology","authors":"Carmine Settembre, Rushika M. Perera","doi":"10.1038/s41580-023-00676-x","DOIUrl":"10.1038/s41580-023-00676-x","url":null,"abstract":"Every cell must satisfy basic requirements for nutrient sensing, utilization and recycling through macromolecular breakdown to coordinate programmes for growth, repair and stress adaptation. The lysosome orchestrates these key functions through the synchronised interplay between hydrolytic enzymes, nutrient transporters and signalling factors, which together enable metabolic coordination with other organelles and regulation of specific gene expression programmes. In this Review, we discuss recent findings on lysosome-dependent signalling pathways, focusing on how the lysosome senses nutrient availability through its physical and functional association with mechanistic target of rapamycin complex 1 (mTORC1) and how, in response, the microphthalmia/transcription factor E (MiT/TFE) transcription factors exert feedback regulation on lysosome biogenesis. We also highlight the emerging interactions of lysosomes with other organelles, which contribute to cellular homeostasis. Lastly, we discuss how lysosome dysfunction contributes to diverse disease pathologies and how inherited mutations that compromise lysosomal hydrolysis, transport or signalling components lead to multi-organ disorders with severe metabolic and neurological impact. A deeper comprehension of lysosomal composition and function, at both the cellular and organismal level, may uncover fundamental insights into human physiology and disease. Lysosomes orchestrate key cellular functions such as nutrient sensing, degradation of macromolecules and stress adaptation. This Review discusses the integration of signalling pathways at the lysosome and highlights the interaction of lysosomes with other organelles and mechanisms that ensure lysosome homeostasis.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138434608","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 : 2023-11-22DOI: 10.1038/s41580-023-00692-x
Florian Heyd
Florian Heyd describes a paper that pointed towards alternative splicing as a driver of human cognitive abilities.
Florian Heyd描述了一篇论文，指出选择性剪接是人类认知能力的驱动因素。
{"title":"Does species-specific alternative splicing make us human?","authors":"Florian Heyd","doi":"10.1038/s41580-023-00692-x","DOIUrl":"10.1038/s41580-023-00692-x","url":null,"abstract":"Florian Heyd describes a paper that pointed towards alternative splicing as a driver of human cognitive abilities.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138293891","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 : 2023-11-13DOI: 10.1038/s41580-023-00673-0
Alex S. Holehouse, Birthe B. Kragelund
Intrinsically disordered protein regions exist in a collection of dynamic interconverting conformations that lack a stable 3D structure. These regions are structurally heterogeneous, ubiquitous and found across all kingdoms of life. Despite the absence of a defined 3D structure, disordered regions are essential for cellular processes ranging from transcriptional control and cell signalling to subcellular organization. Through their conformational malleability and adaptability, disordered regions extend the repertoire of macromolecular interactions and are readily tunable by their structural and chemical context, making them ideal responders to regulatory cues. Recent work has led to major advances in understanding the link between protein sequence and conformational behaviour in disordered regions, yet the link between sequence and molecular function is less well defined. Here we consider the biochemical and biophysical foundations that underlie how and why disordered regions can engage in productive cellular functions, provide examples of emerging concepts and discuss how protein disorder contributes to intracellular information processing and regulation of cellular function. Intrinsically disordered regions of proteins lack a defined 3D structure and exist in a collection of interconverting conformations. Recent work is shedding light on how — through their conformational malleability and adaptability — intrinsically disordered regions extend the repertoire of macromolecular interactions in the cell and contribute to key cellular functions.
{"title":"The molecular basis for cellular function of intrinsically disordered protein regions","authors":"Alex S. Holehouse, Birthe B. Kragelund","doi":"10.1038/s41580-023-00673-0","DOIUrl":"10.1038/s41580-023-00673-0","url":null,"abstract":"Intrinsically disordered protein regions exist in a collection of dynamic interconverting conformations that lack a stable 3D structure. These regions are structurally heterogeneous, ubiquitous and found across all kingdoms of life. Despite the absence of a defined 3D structure, disordered regions are essential for cellular processes ranging from transcriptional control and cell signalling to subcellular organization. Through their conformational malleability and adaptability, disordered regions extend the repertoire of macromolecular interactions and are readily tunable by their structural and chemical context, making them ideal responders to regulatory cues. Recent work has led to major advances in understanding the link between protein sequence and conformational behaviour in disordered regions, yet the link between sequence and molecular function is less well defined. Here we consider the biochemical and biophysical foundations that underlie how and why disordered regions can engage in productive cellular functions, provide examples of emerging concepts and discuss how protein disorder contributes to intracellular information processing and regulation of cellular function. Intrinsically disordered regions of proteins lack a defined 3D structure and exist in a collection of interconverting conformations. Recent work is shedding light on how — through their conformational malleability and adaptability — intrinsically disordered regions extend the repertoire of macromolecular interactions in the cell and contribute to key cellular functions.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91398643","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 : 2023-11-13DOI: 10.1038/s41580-023-00687-8
Manuela Richter
In this Tools of the Trade article, Manuela Richter (Dumont lab) describes a method to probe mechanisms of cytoskeletal network re-organization that uses a targeted laser to both trigger network remodelling and track network dynamics.
{"title":"Probing cytoskeletal remodelling by cutting and marking filaments","authors":"Manuela Richter","doi":"10.1038/s41580-023-00687-8","DOIUrl":"10.1038/s41580-023-00687-8","url":null,"abstract":"In this Tools of the Trade article, Manuela Richter (Dumont lab) describes a method to probe mechanisms of cytoskeletal network re-organization that uses a targeted laser to both trigger network remodelling and track network dynamics.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91398644","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 : 2023-11-07DOI: 10.1038/s41580-023-00685-w
Emily Wong
Emily Wong describes a study that provided a quantitative methodology for analyzing ChIP experiments and shifted our understanding of the functionality of transcription factors.
{"title":"The nuance in DNA and transcription factor interactions","authors":"Emily Wong","doi":"10.1038/s41580-023-00685-w","DOIUrl":"10.1038/s41580-023-00685-w","url":null,"abstract":"Emily Wong describes a study that provided a quantitative methodology for analyzing ChIP experiments and shifted our understanding of the functionality of transcription factors.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483977","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 : 2023-11-01DOI: 10.1038/s41580-023-00684-x
Paulina Strzyz
Yu et al. identify senescent cells as important players in the regeneration of complex structures.
Yu 等人发现衰老细胞是复杂结构再生过程中的重要角色。
{"title":"Senescent cells support limb regeneration","authors":"Paulina Strzyz","doi":"10.1038/s41580-023-00684-x","DOIUrl":"10.1038/s41580-023-00684-x","url":null,"abstract":"Yu et al. identify senescent cells as important players in the regeneration of complex structures.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425178","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 : 2023-11-01DOI: 10.1038/s41580-023-00681-0
Bohan Zhang
In this Tools of the Trade article, Bohan Zhang (Gladyshev lab) discusses how the use of extended heterochronic parabiosis in mice (surgical connection between circulatory systems for an extended period), followed by detachment, can shed light on potential mechanisms that reverse mammalian ageing.
在这篇 "贸易工具"（Tools of the Trade）文章中，张博涵（格拉迪舍夫实验室）讨论了如何利用延长小鼠异时同种异体培养（通过手术将循环系统连接一段较长的时间），然后再进行分离，从而揭示逆转哺乳动物衰老的潜在机制。
{"title":"Extended heterochronic parabiosis as an approach to study rejuvenation","authors":"Bohan Zhang","doi":"10.1038/s41580-023-00681-0","DOIUrl":"10.1038/s41580-023-00681-0","url":null,"abstract":"In this Tools of the Trade article, Bohan Zhang (Gladyshev lab) discusses how the use of extended heterochronic parabiosis in mice (surgical connection between circulatory systems for an extended period), followed by detachment, can shed light on potential mechanisms that reverse mammalian ageing.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425177","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 : 2023-10-30DOI: 10.1038/s41580-023-00662-3
Bing Zhang, Ting Chen
Hair follicles are essential appendages of the mammalian skin, as hair performs vital functions of protection, thermoregulation and sensation. Hair follicles harbour exceptional regenerative abilities as they contain multiple somatic stem cell populations such as hair follicle stem cells (HFSCs) and melanocyte stem cells. Surrounding the stem cells and their progeny, diverse groups of cells and extracellular matrix proteins are organized to form a microenvironment (called ‘niche’) that serves to promote and maintain the optimal functioning of these stem cell populations. Recent studies have shed light on the intricate nature of the HFSC niche and its crucial role in regulating hair follicle regeneration. In this Review, we describe how the niche serves as a signalling hub, communicating, deciphering and integrating both local signals within the skin and systemic inputs from the body and environment to modulate HFSC activity. We delve into the recent advancements in identifying the cellular and molecular nature of the niche, providing a holistic perspective on its essential functions in hair follicle morphogenesis, regeneration and ageing. The regenerative abilities of mammalian hair follicles are facilitated by the proliferation of hair follicle stem cells (HFSCs), which reside in specialized niches within the skin. Recent studies shed light on how local signals and systemic inputs from the body and the environment regulate HFSC function.
{"title":"Local and systemic mechanisms that control the hair follicle stem cell niche","authors":"Bing Zhang, Ting Chen","doi":"10.1038/s41580-023-00662-3","DOIUrl":"10.1038/s41580-023-00662-3","url":null,"abstract":"Hair follicles are essential appendages of the mammalian skin, as hair performs vital functions of protection, thermoregulation and sensation. Hair follicles harbour exceptional regenerative abilities as they contain multiple somatic stem cell populations such as hair follicle stem cells (HFSCs) and melanocyte stem cells. Surrounding the stem cells and their progeny, diverse groups of cells and extracellular matrix proteins are organized to form a microenvironment (called ‘niche’) that serves to promote and maintain the optimal functioning of these stem cell populations. Recent studies have shed light on the intricate nature of the HFSC niche and its crucial role in regulating hair follicle regeneration. In this Review, we describe how the niche serves as a signalling hub, communicating, deciphering and integrating both local signals within the skin and systemic inputs from the body and environment to modulate HFSC activity. We delve into the recent advancements in identifying the cellular and molecular nature of the niche, providing a holistic perspective on its essential functions in hair follicle morphogenesis, regeneration and ageing. The regenerative abilities of mammalian hair follicles are facilitated by the proliferation of hair follicle stem cells (HFSCs), which reside in specialized niches within the skin. Recent studies shed light on how local signals and systemic inputs from the body and the environment regulate HFSC function.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":112.7,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413178","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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