Nature Reviews Molecular Cell Biology最新文献_第6页

Transcription regulation by biomolecular condensates 生物分子凝聚体的转录调控

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-11-08 DOI: 10.1038/s41580-024-00789-x

Gaofeng Pei, Heankel Lyons, Pilong Li, Benjamin R. Sabari

{"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}

引用次数: 0

Homeostasis control in health and disease by the unfolded protein response 未折叠蛋白反应对健康和疾病的平衡控制

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-11-05 DOI: 10.1038/s41580-024-00794-0

Diego Acosta-Alvear, Jonathan M. Harnoss, Peter Walter, Avi Ashkenazi

{"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}

引用次数: 0

Epigenetic discovery by enzyme activity profiling 通过酶活性分析发现表观遗传学

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-25 DOI: 10.1038/s41580-024-00801-4

Manini S. Penikalapati, Jordan L. Meier

引用次数: 0

The double-edged sword of eliminating senescent cells 消除衰老细胞的双刃剑

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-24 DOI: 10.1038/s41580-024-00798-w

Eric Gilson

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When senescence generates pluripotent stem cells 当衰老产生多能干细胞时

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-24 DOI: 10.1038/s41580-024-00799-9

Miria Ricchetti

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A nuclear morphology-based machine learning algorithm for senescence detection 基于核形态学的衰老检测机器学习算法

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-23 DOI: 10.1038/s41580-024-00796-y

Imanol Duran

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The prompt to discover senolytics 发现老年痴呆症的提示

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-23 DOI: 10.1038/s41580-024-00795-z

James L. Kirkland

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All the sites we cannot see: Sources and mitigation of false negatives in RNA modification studies 我们看不到的所有位点RNA 修饰研究中假阴性的来源与缓解

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-21 DOI: 10.1038/s41580-024-00784-2

Shalini Oberdoerffer, Wendy V. Gilbert

{"title":"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/s41580-024-00784-2","DOIUrl":"10.1038/s41580-024-00784-2","url":null,"abstract":"RNA modifications are essential for human health — too much or too little of them leads to serious illnesses ranging from neurodevelopmental disorders to cancer. Technical advances in RNA modification sequencing are beginning to uncover the RNA targets of diverse RNA-modifying enzymes that are dysregulated in disease. However, the emerging transcriptome-wide maps of modified nucleosides installed by these enzymes should be considered as first drafts. In particular, a range of technical artefacts lead to false negatives — modified sites that are overlooked owing to technique-dependent, and often sequence-context-specific, ‘blind spots’. In this Review, we discuss potential sources of false negatives in sequencing-based RNA modification maps, propose mitigation strategies and suggest guidelines for transparent reporting of sensitivity to detect modified sites in profiling studies. Important considerations for recognition and avoidance of false negatives include assessment and reporting of position-specific sequencing depth, identification of protocol-dependent RNA capture biases and applying controls for false negatives as well as for false positives. Despite their limitations, emerging maps of RNA modifications reveal exciting and largely uncharted potential for post-transcriptional control of all aspects of RNA function. Specialized RNA modification sequencing techniques are helping to uncover how dysregulation of RNA modification leads to disease. This Review discusses how technical artefacts can cause false negatives (overlooked modified sites) in RNA modification maps, proposes mitigation strategies and suggests guidelines for detection-sensitivity reporting.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 3","pages":"237-248"},"PeriodicalIF":81.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451812","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}

引用次数: 0

Molecular mechanisms of mitochondrial dynamics 线粒体动力学的分子机制

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-17 DOI: 10.1038/s41580-024-00785-1

Luis-Carlos Tábara, Mayuko Segawa, Julien Prudent

{"title":"Molecular mechanisms of mitochondrial dynamics","authors":"Luis-Carlos Tábara, Mayuko Segawa, Julien Prudent","doi":"10.1038/s41580-024-00785-1","DOIUrl":"10.1038/s41580-024-00785-1","url":null,"abstract":"Mitochondria not only synthesize energy required for cellular functions but are also involved in numerous cellular pathways including apoptosis, calcium homoeostasis, inflammation and immunity. Mitochondria are dynamic organelles that undergo cycles of fission and fusion, and these transitions between fragmented and hyperfused networks ensure mitochondrial function, enabling adaptations to metabolic changes or cellular stress. Defects in mitochondrial morphology have been associated with numerous diseases, highlighting the importance of elucidating the molecular mechanisms regulating mitochondrial morphology. Here, we discuss recent structural insights into the assembly and mechanism of action of the core mitochondrial dynamics proteins, such as the dynamin-related protein 1 (DRP1) that controls division, and the mitofusins (MFN1 and MFN2) and optic atrophy 1 (OPA1) driving membrane fusion. Furthermore, we provide an updated view of the complex interplay between different proteins, lipids and organelles during the processes of mitochondrial membrane fusion and fission. Overall, we aim to present a valuable framework reflecting current perspectives on how mitochondrial membrane remodelling is regulated. Mitochondrial fusion and fission events are tightly regulated by core mitochondrial dynamics proteins. Recent structural and functional findings have characterized how these proteins interact with each other, with the mitochondrial membrane and with other organelles to guide membrane remodelling.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 2","pages":"123-146"},"PeriodicalIF":81.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448321","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}

引用次数: 0

Goodbye, senescent cells: CAR-T cells unleashed to fight ageing 再见了，衰老的细胞释放 CAR-T 细胞，对抗衰老

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-16 DOI: 10.1038/s41580-024-00792-2

Raffaella Di Micco

引用次数: 0