{"title":"The centromere as a tag of self-DNA","authors":"Ruth Kroschewski","doi":"10.1038/s41580-025-00827-2","DOIUrl":"10.1038/s41580-025-00827-2","url":null,"abstract":"Intriguing findings in yeast suggested that centromeres ‘tag’ DNA as self and allow its condensation during mitosis; vice versa, if a certain DNA is condensed during mitosis, it harbours a centromere.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 3","pages":"172-172"},"PeriodicalIF":81.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055051","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}
Jesus M. Gomez-Salinero, David Redmond, Shahin Rafii
{"title":"Microenvironmental determinants of endothelial cell heterogeneity","authors":"Jesus M. Gomez-Salinero, David Redmond, Shahin Rafii","doi":"10.1038/s41580-024-00825-w","DOIUrl":"https://doi.org/10.1038/s41580-024-00825-w","url":null,"abstract":"<p>During development, endothelial cells (ECs) undergo an extraordinary specialization by which generic capillary microcirculatory networks spanning from arteries to veins transform into patterned organotypic zonated blood vessels. These capillary ECs become specialized to support the cellular and metabolic demands of each specific organ, including supplying tissue-specific angiocrine factors that orchestrate organ development, maintenance of organ-specific functions and regeneration of injured adult organs. Here, we illustrate the mechanisms by which microenvironmental signals emanating from non-vascular niche cells induce generic ECs to acquire specific inter-organ and intra-organ functional attributes. We describe how perivascular, parenchymal and immune cells dictate vascular heterogeneity and capillary zonation, and how this system is maintained through tissue-specific signalling activated by vasculogenic and angiogenic factors and deposition of matrix components. We also discuss how perturbation of organotypic vascular niche cues lead to erasure of EC signatures, contributing to the pathogenesis of disease processes. We also describe approaches that use reconstitution of tissue-specific signatures of ECs to promote regeneration of damaged organs.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"35 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049942","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}
Benjamín Cartes-Saavedra, Arijita Ghosh, György Hajnóczky
{"title":"The roles of mitochondria in global and local intracellular calcium signalling","authors":"Benjamín Cartes-Saavedra, Arijita Ghosh, György Hajnóczky","doi":"10.1038/s41580-024-00820-1","DOIUrl":"https://doi.org/10.1038/s41580-024-00820-1","url":null,"abstract":"<p>Activation of Ca<sup>2+</sup> channels in Ca<sup>2+</sup> stores in organelles and the plasma membrane generates cytoplasmic calcium ([Ca<sup>2+</sup>]<sub>c</sub>) signals that control almost every aspect of cell function, including metabolism, vesicle fusion and contraction. Mitochondria have a high capacity for Ca<sup>2+</sup> uptake and chelation, alongside efficient Ca<sup>2+</sup> release mechanisms. Still, mitochondria do not store Ca<sup>2+</sup> in a prolonged manner under physiological conditions and lack the capacity to generate global [Ca<sup>2+</sup>]<sub>c</sub> signals. However, mitochondria take up Ca<sup>2+</sup> at high local [Ca<sup>2+</sup>]<sub>c</sub> signals that originate from neighbouring organelles, and also during sustained global elevations of [Ca<sup>2+</sup>]<sub>c</sub>. Accumulated Ca<sup>2+</sup> in the mitochondria stimulates oxidative metabolism and upon return to the cytoplasm, can produce spatially confined rises in [Ca<sup>2+</sup>]<sub>c</sub> to exert control over processes that are sensitive to Ca<sup>2+</sup>. Thus, the mitochondrial handling of [Ca<sup>2+</sup>]<sub>c</sub> is of physiological relevance. Furthermore, dysregulation of mitochondrial Ca<sup>2+</sup> handling can contribute to debilitating diseases. We discuss the mechanisms and relevance of mitochondria in local and global calcium signals.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"20 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044165","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}
{"title":"Mechanistic insights into Wnt–β-catenin pathway activation and signal transduction","authors":"Madelon M. Maurice, Stephane Angers","doi":"10.1038/s41580-024-00823-y","DOIUrl":"10.1038/s41580-024-00823-y","url":null,"abstract":"In multicellular organisms, Wnt proteins govern stem and progenitor cell renewal and differentiation to regulate embryonic development, adult tissue homeostasis and tissue regeneration. Defects in canonical Wnt signalling, which is transduced intracellularly by β-catenin, have been associated with developmental disorders, degenerative diseases and cancers. Although a simple model describing Wnt–β-catenin signalling is widely used to introduce this pathway and has largely remained unchanged over the past 30 years, in this Review we discuss recent studies that have provided important new insights into the mechanisms of Wnt production, receptor activation and intracellular signalling that advance our understanding of the molecular mechanisms that underlie this important cell–cell communication system. In addition, we review the recent development of molecules capable of activating the Wnt–β-catenin pathway with selectivity in vitro and in vivo that is enabling new lines of study to pave the way for the development of Wnt therapies for the treatment of human diseases. Wnt–β-catenin signalling regulates stem cell renewal, development and tissue homeostasis. In this Review, the authors examine recent findings concerning Wnt protein production, receptor activation and intracellular signalling, focusing on the regulation of the β-catenin destruction complex.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 5","pages":"371-388"},"PeriodicalIF":81.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026720","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}
{"title":"A guide to the biogenesis and functions of endogenous small non-coding RNAs in animals","authors":"Karina Jouravleva, Phillip D. Zamore","doi":"10.1038/s41580-024-00818-9","DOIUrl":"10.1038/s41580-024-00818-9","url":null,"abstract":"Small non-coding RNAs can be categorized into two main classes: structural RNAs and regulatory RNAs. Structural RNAs, which are abundant and ubiquitously expressed, have essential roles in the maturation of pre-mRNAs, modification of rRNAs and the translation of coding transcripts. By contrast, regulatory RNAs are often expressed in a developmental-specific, tissue-specific or cell-type-specific manner and exert precise control over gene expression. Reductions in cost and improvements in the accuracy of high-throughput RNA sequencing have led to the identification of many new small RNA species. In this Review, we provide a broad discussion of the genomic origins, biogenesis and functions of structural small RNAs, including tRNAs, small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), vault RNAs (vtRNAs) and Y RNAs as well as their derived RNA fragments, and of regulatory small RNAs, such as microRNAs (miRNAs), endogenous small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs), in animals. Many new small RNA species and their derived fragments have been recently identified in animals. This Review discusses the biogenesis and functions of both structural small RNAs, such as tRNAs and small nuclear RNAs (snRNAs), and of regulatory small RNAs such as microRNAs and PIWI-interacting RNAs (piRNAs).","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 5","pages":"347-370"},"PeriodicalIF":81.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030728","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}
{"title":"Sequencing technologies to measure translation in single cells","authors":"Michael VanInsberghe, Alexander van Oudenaarden","doi":"10.1038/s41580-024-00822-z","DOIUrl":"10.1038/s41580-024-00822-z","url":null,"abstract":"Translation is one of the most energy-intensive processes in a cell and, accordingly, is tightly regulated. Genome-wide methods to measure translation and the translatome and to study the complex regulation of protein synthesis have enabled unprecedented characterization of this crucial step of gene expression. However, technological limitations have hampered our understanding of translation control in multicellular tissues, rare cell types and dynamic cellular processes. Recent optimizations, adaptations and new techniques have enabled these measurements to be made at single-cell resolution. In this Progress, we discuss single-cell sequencing technologies to measure translation, including ribosome profiling, ribosome affinity purification and spatial translatome methods. Recent sequencing-based methods, including novel ribosome profiling, ribosome affinity purification and spatial translation methods, have enabled the measurement of translation at single-cell resolution. These developments have opened avenues for studying translation regulation in tissues and rare cell types.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 5","pages":"337-346"},"PeriodicalIF":81.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989980","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}
{"title":"Proteins that assemble co-translationally lean on their partner for stability","authors":"Kim Baumann","doi":"10.1038/s41580-024-00824-x","DOIUrl":"10.1038/s41580-024-00824-x","url":null,"abstract":"This study provides a framework to predict whether protein complexes assemble co- or post-translationally based solely on protein structures.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 2","pages":"85-85"},"PeriodicalIF":81.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934993","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}
{"title":"Genome characteristics at the borders","authors":"Marina Lusic","doi":"10.1038/s41580-024-00819-8","DOIUrl":"10.1038/s41580-024-00819-8","url":null,"abstract":"Marina Lusic recounts seminal papers that showed that nuclear pore complexes and association with the nuclear lamina can shape borders between genomic domains and gene regulation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 3","pages":"171-171"},"PeriodicalIF":81.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929710","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}
Thomas Mortimer, Jacob G. Smith, Pura Muñoz-Cánoves, Salvador Aznar Benitah
{"title":"Circadian clock communication during homeostasis and ageing","authors":"Thomas Mortimer, Jacob G. Smith, Pura Muñoz-Cánoves, Salvador Aznar Benitah","doi":"10.1038/s41580-024-00802-3","DOIUrl":"10.1038/s41580-024-00802-3","url":null,"abstract":"Maintaining homeostasis is essential for continued health, and the progressive decay of homeostatic processes is a hallmark of ageing. Daily environmental rhythms threaten homeostasis, and circadian clocks have evolved to execute physiological processes in a manner that anticipates, and thus mitigates, their effects on the organism. Clocks are active in almost all cell types; their rhythmicity and functional output are determined by a combination of tissue-intrinsic and systemic inputs. Numerous inputs for a specific tissue are produced by the activity of circadian clocks of other tissues or cell types, generating a form of crosstalk known as clock communication. In mammals, the central clock in the hypothalamus integrates signals from external light–dark cycles to align peripheral clocks elsewhere in the body. This regulation is complemented by a tissue-specific milieu of external, systemic and niche inputs that modulate and cooperate with the cellular circadian clock machinery of a tissue to tailor its functional output. These mechanisms of clock communication decay during ageing, and growing evidence suggests that this decline might drive ageing-related morbidities. Dietary, behavioural and pharmacological interventions may offer the possibility to overcome these changes and in turn improve healthspan. Communication between the circadian clocks of different cell and tissue types supports the daily rhythms of homeostatic processes that maintain bodily health. Ageing leads to a decline in this complex communication network to the detriment of these daily homeostatic rhythms. This Review discusses clock communication pathways in the healthy versus aged state and explores the potential of modulating these communication pathways to slow circadian rhythm decline with ageing.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 4","pages":"314-331"},"PeriodicalIF":81.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916955","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}
{"title":"The biogenesis and regulation of animal microRNAs","authors":"Haedong Kim, Young-Yoon Lee, V. Narry Kim","doi":"10.1038/s41580-024-00805-0","DOIUrl":"10.1038/s41580-024-00805-0","url":null,"abstract":"MicroRNAs (miRNAs) are small, yet profoundly influential, non-coding RNAs that base-pair with mRNAs to induce RNA silencing. Although the basic principles of miRNA biogenesis and function have been established, recent breakthroughs have yielded important new insights into the molecular mechanisms of miRNA biogenesis. In this Review, we discuss the metazoan miRNA biogenesis pathway step-by-step, focusing on the key biogenesis machinery, including the Drosha–DGCR8 complex (Microprocessor), exportin-5, Dicer and Argonaute. We also highlight newly identified cis-acting elements and their impact on miRNA maturation, informed by advanced high-throughput and structural studies, and discuss recently discovered mechanisms of clustered miRNA processing, target recognition and target-directed miRNA decay (TDMD). Lastly, we explore multiple regulatory layers of miRNA biogenesis, mediated by RNA–protein interactions, miRNA tailing (uridylation or adenylation) and RNA modifications. MicroRNAs (miRNAs) are small non-coding RNAs that induce RNA silencing. Advances in high-throughput and structural studies have provided new insights into animal miRNA biogenesis mediated by RNA–protein interactions, miRNA tailing (uridylation or adenylation) and RNA modifications, and have increased our understanding of miRNA target recognition and target-directed miRNA decay.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 4","pages":"276-296"},"PeriodicalIF":81.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848995","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}