Pub Date : 2024-11-15DOI: 10.1038/s41580-024-00807-y
Rachael Hamby, Qiang Cai, Hailing Jin
Evidence shows that RNA trafficking is a key communication mechanism across kingdoms and species, but how RNAs are secreted and trafficked and how they function within the recipient organisms remain unclear. Here, we discuss how understanding inter-organismal RNA communication can assist in disease management in both agriculture and medicine. Cross-species host–pathogen or mutualistic RNA communication, especially through extracellular vesicles, can have important applications, including gene silencing in agriculture and RNA-based therapeutics.
{"title":"RNA communication between organisms inspires innovative eco-friendly strategies for disease control","authors":"Rachael Hamby, Qiang Cai, Hailing Jin","doi":"10.1038/s41580-024-00807-y","DOIUrl":"10.1038/s41580-024-00807-y","url":null,"abstract":"Evidence shows that RNA trafficking is a key communication mechanism across kingdoms and species, but how RNAs are secreted and trafficked and how they function within the recipient organisms remain unclear. Here, we discuss how understanding inter-organismal RNA communication can assist in disease management in both agriculture and medicine. Cross-species host–pathogen or mutualistic RNA communication, especially through extracellular vesicles, can have important applications, including gene silencing in agriculture and RNA-based therapeutics.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 2","pages":"81-82"},"PeriodicalIF":81.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637257","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 : 2024-11-14DOI: 10.1038/s41580-024-00806-z
Valerie A. Tornini
Valerie Tornini discusses two studies that identified functional roles for small proteins encoded by short open reading frames, and highlights the potential for this research field in fundamental and clinical research.
{"title":"Grand roles for microproteins","authors":"Valerie A. Tornini","doi":"10.1038/s41580-024-00806-z","DOIUrl":"10.1038/s41580-024-00806-z","url":null,"abstract":"Valerie Tornini discusses two studies that identified functional roles for small proteins encoded by short open reading frames, and highlights the potential for this research field in fundamental and clinical research.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 2","pages":"84-84"},"PeriodicalIF":81.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610084","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 : 2024-11-13DOI: 10.1038/s41580-024-00797-x
Samuel E. Lacey, Gaia Pigino
Primary and motile cilia are eukaryotic organelles that perform crucial roles in cellular signalling and motility. Intraflagellar transport (IFT) contributes to the formation of the highly specialized ciliary proteome by active and selective transport of soluble and membrane proteins into and out of cilia. IFT is performed by the IFT-A and IFT-B protein complexes, which together link cargoes to the microtubule motors kinesin and dynein. In this Review, we discuss recent structural and mechanistic insights on how the IFT complexes are first recruited to the base of the cilium, how they polymerize into an anterograde IFT train, and how this complex imports cargoes from the cytoplasm. We will describe insights into how kinesin-driven anterograde trains are carried to the ciliary tip, where they are remodelled into dynein-driven retrograde trains for cargo export. We will also present how the interplay between IFT-A and IFT-B complexes, motor proteins and cargo adaptors is regulated for bidirectional ciliary transport. Intraflagellar transport (IFT) ensures delivery of selected proteins into cilia. The IFT protein complexes IFT-A and IFT-B polymerize at the base of the cilium to form an anterograde train that facilitates cargo import, whereas remodelling into a retrograde train at the ciliary tip enables cargo export.
{"title":"The intraflagellar transport cycle","authors":"Samuel E. Lacey, Gaia Pigino","doi":"10.1038/s41580-024-00797-x","DOIUrl":"10.1038/s41580-024-00797-x","url":null,"abstract":"Primary and motile cilia are eukaryotic organelles that perform crucial roles in cellular signalling and motility. Intraflagellar transport (IFT) contributes to the formation of the highly specialized ciliary proteome by active and selective transport of soluble and membrane proteins into and out of cilia. IFT is performed by the IFT-A and IFT-B protein complexes, which together link cargoes to the microtubule motors kinesin and dynein. In this Review, we discuss recent structural and mechanistic insights on how the IFT complexes are first recruited to the base of the cilium, how they polymerize into an anterograde IFT train, and how this complex imports cargoes from the cytoplasm. We will describe insights into how kinesin-driven anterograde trains are carried to the ciliary tip, where they are remodelled into dynein-driven retrograde trains for cargo export. We will also present how the interplay between IFT-A and IFT-B complexes, motor proteins and cargo adaptors is regulated for bidirectional ciliary transport. Intraflagellar transport (IFT) ensures delivery of selected proteins into cilia. The IFT protein complexes IFT-A and IFT-B polymerize at the base of the cilium to form an anterograde train that facilitates cargo import, whereas remodelling into a retrograde train at the ciliary tip enables cargo export.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 3","pages":"175-192"},"PeriodicalIF":81.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609901","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 : 2024-11-12DOI: 10.1038/s41580-024-00810-3
Shalini Oberdoerffer, Wendy V. Gilbert
{"title":"Author Correction: All the sites we cannot see: Sources and mitigation of false negatives in RNA modification studies","authors":"Shalini Oberdoerffer, Wendy V. Gilbert","doi":"10.1038/s41580-024-00810-3","DOIUrl":"10.1038/s41580-024-00810-3","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 3","pages":"249-249"},"PeriodicalIF":81.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41580-024-00810-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-08DOI: 10.1038/s41580-024-00789-x
Gaofeng Pei, Heankel Lyons, Pilong Li, Benjamin R. Sabari
Biomolecular condensates regulate transcription by dynamically compartmentalizing the transcription machinery. Classic models of transcription regulation focus on the recruitment and regulation of RNA polymerase II by the formation of complexes at the 1–10 nm length scale, which are driven by structured and stoichiometric interactions. These complexes are further organized into condensates at the 100–1,000 nm length scale, which are driven by dynamic multivalent interactions often involving domain–ligand pairs or intrinsically disordered regions. Regulation through condensate-mediated organization does not supersede the processes occurring at the 1–10 nm scale, but it provides regulatory mechanisms for promoting or preventing these processes in the crowded nuclear environment. Regulation of transcription by transcriptional condensates is involved in cell state transitions during animal and plant development, cell signalling and cellular responses to the environment. These condensate-mediated processes are dysregulated in developmental disorders, cancer and neurodegeneration. In this Review, we discuss the principles underlying the regulation of transcriptional condensates, their roles in physiology and their dysregulation in human diseases. Transcriptional condensates, which are formed through dynamic multivalent interactions between proteins, RNA and chromatin, regulate transcription by compartmentalizing its machinery in the crowded nuclear environment. These condensates regulate animal and plant development, cell signalling and responses to the environment, and they are dysregulated in developmental disorders, cancer and neurodegeneration.
{"title":"Transcription regulation by biomolecular condensates","authors":"Gaofeng Pei, Heankel Lyons, Pilong Li, Benjamin R. Sabari","doi":"10.1038/s41580-024-00789-x","DOIUrl":"10.1038/s41580-024-00789-x","url":null,"abstract":"Biomolecular condensates regulate transcription by dynamically compartmentalizing the transcription machinery. Classic models of transcription regulation focus on the recruitment and regulation of RNA polymerase II by the formation of complexes at the 1–10 nm length scale, which are driven by structured and stoichiometric interactions. These complexes are further organized into condensates at the 100–1,000 nm length scale, which are driven by dynamic multivalent interactions often involving domain–ligand pairs or intrinsically disordered regions. Regulation through condensate-mediated organization does not supersede the processes occurring at the 1–10 nm scale, but it provides regulatory mechanisms for promoting or preventing these processes in the crowded nuclear environment. Regulation of transcription by transcriptional condensates is involved in cell state transitions during animal and plant development, cell signalling and cellular responses to the environment. These condensate-mediated processes are dysregulated in developmental disorders, cancer and neurodegeneration. In this Review, we discuss the principles underlying the regulation of transcriptional condensates, their roles in physiology and their dysregulation in human diseases. Transcriptional condensates, which are formed through dynamic multivalent interactions between proteins, RNA and chromatin, regulate transcription by compartmentalizing its machinery in the crowded nuclear environment. These condensates regulate animal and plant development, cell signalling and responses to the environment, and they are dysregulated in developmental disorders, cancer and neurodegeneration.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 3","pages":"213-236"},"PeriodicalIF":81.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596850","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 : 2024-11-05DOI: 10.1038/s41580-024-00794-0
Diego Acosta-Alvear, Jonathan M. Harnoss, Peter Walter, Avi Ashkenazi
Cells rely on the endoplasmic reticulum (ER) to fold and assemble newly synthesized transmembrane and secretory proteins — essential for cellular structure–function and for both intracellular and intercellular communication. To ensure the operative fidelity of the ER, eukaryotic cells leverage the unfolded protein response (UPR) — a stress-sensing and signalling network that maintains homeostasis by rebalancing the biosynthetic capacity of the ER according to need. The metazoan UPR can also redirect signalling from cytoprotective adaptation to programmed cell death if homeostasis restoration fails. As such, the UPR benefits multicellular organisms by preserving optimally functioning cells while removing damaged ones. Nevertheless, dysregulation of the UPR can be harmful. In this Review, we discuss the UPR and its regulatory processes as a paradigm in health and disease. We highlight important recent advances in molecular and mechanistic understanding of the UPR that enable greater precision in designing and developing innovative strategies to harness its potential for therapeutic gain. We underscore the rheostatic character of the UPR, its contextual nature and critical open questions for its further elucidation. The unfolded protein response is a stress-sensing and signalling network that maintains homeostasis by regulating the biosynthetic capacity of the endoplasmic reticulum and induces cell death when homeostasis is not restored. This Review discusses the mechanisms of action of the UPR, its interactions with other cellular processes, roles in disease and possible therapeutic interventions.
{"title":"Homeostasis control in health and disease by the unfolded protein response","authors":"Diego Acosta-Alvear, Jonathan M. Harnoss, Peter Walter, Avi Ashkenazi","doi":"10.1038/s41580-024-00794-0","DOIUrl":"10.1038/s41580-024-00794-0","url":null,"abstract":"Cells rely on the endoplasmic reticulum (ER) to fold and assemble newly synthesized transmembrane and secretory proteins — essential for cellular structure–function and for both intracellular and intercellular communication. To ensure the operative fidelity of the ER, eukaryotic cells leverage the unfolded protein response (UPR) — a stress-sensing and signalling network that maintains homeostasis by rebalancing the biosynthetic capacity of the ER according to need. The metazoan UPR can also redirect signalling from cytoprotective adaptation to programmed cell death if homeostasis restoration fails. As such, the UPR benefits multicellular organisms by preserving optimally functioning cells while removing damaged ones. Nevertheless, dysregulation of the UPR can be harmful. In this Review, we discuss the UPR and its regulatory processes as a paradigm in health and disease. We highlight important recent advances in molecular and mechanistic understanding of the UPR that enable greater precision in designing and developing innovative strategies to harness its potential for therapeutic gain. We underscore the rheostatic character of the UPR, its contextual nature and critical open questions for its further elucidation. The unfolded protein response is a stress-sensing and signalling network that maintains homeostasis by regulating the biosynthetic capacity of the endoplasmic reticulum and induces cell death when homeostasis is not restored. This Review discusses the mechanisms of action of the UPR, its interactions with other cellular processes, roles in disease and possible therapeutic interventions.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 3","pages":"193-212"},"PeriodicalIF":81.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580710","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 : 2024-10-25DOI: 10.1038/s41580-024-00801-4
Manini S. Penikalapati, Jordan L. Meier
C. David Allis’s discovery of the first histone acetyltransferase from Tetrahymena exemplifies an approach that continues to evolve and now has a crucial role in drug development.
{"title":"Epigenetic discovery by enzyme activity profiling","authors":"Manini S. Penikalapati, Jordan L. Meier","doi":"10.1038/s41580-024-00801-4","DOIUrl":"10.1038/s41580-024-00801-4","url":null,"abstract":"C. David Allis’s discovery of the first histone acetyltransferase from Tetrahymena exemplifies an approach that continues to evolve and now has a crucial role in drug development.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 2","pages":"83-83"},"PeriodicalIF":81.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489501","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 : 2024-10-24DOI: 10.1038/s41580-024-00798-w
Eric Gilson
Removal of different types of senescent cells can be either beneficial or detrimental to health, with potential consequences to senotherapies.
清除不同类型的衰老细胞可能对健康有益，也可能有害，从而对衰老疗法产生潜在影响。
{"title":"The double-edged sword of eliminating senescent cells","authors":"Eric Gilson","doi":"10.1038/s41580-024-00798-w","DOIUrl":"10.1038/s41580-024-00798-w","url":null,"abstract":"Removal of different types of senescent cells can be either beneficial or detrimental to health, with potential consequences to senotherapies.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 12","pages":"957-957"},"PeriodicalIF":81.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489008","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 : 2024-10-24DOI: 10.1038/s41580-024-00799-9
Miria Ricchetti
Senescent cells in the amputated head of the cnidarian Hydractinia symbiolongicarpus drive the reprogramming of somatic cells into pluripotent stem cells, which are required for full body regeneration.
{"title":"When senescence generates pluripotent stem cells","authors":"Miria Ricchetti","doi":"10.1038/s41580-024-00799-9","DOIUrl":"10.1038/s41580-024-00799-9","url":null,"abstract":"Senescent cells in the amputated head of the cnidarian Hydractinia symbiolongicarpus drive the reprogramming of somatic cells into pluripotent stem cells, which are required for full body regeneration.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 12","pages":"952-952"},"PeriodicalIF":81.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489007","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 : 2024-10-23DOI: 10.1038/s41580-024-00796-y
Imanol Duran
In this Tools of the Trade article, Duran (Gil lab) describes the development of novel machine learning algorithms that enable the detection of senescent cells in vitro and in diverse tissues based solely on nuclear morphologeny analysis.
在这篇《贸易工具》（Tools of the Trade）文章中，Duran（Gil 实验室）介绍了新型机器学习算法的开发情况，该算法能够仅根据核形态学分析检测体外和不同组织中的衰老细胞。
{"title":"A nuclear morphology-based machine learning algorithm for senescence detection","authors":"Imanol Duran","doi":"10.1038/s41580-024-00796-y","DOIUrl":"10.1038/s41580-024-00796-y","url":null,"abstract":"In this Tools of the Trade article, Duran (Gil lab) describes the development of novel machine learning algorithms that enable the detection of senescent cells in vitro and in diverse tissues based solely on nuclear morphologeny analysis.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 12","pages":"949-949"},"PeriodicalIF":81.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487356","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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