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Mechanistic insights into Wnt–β-catenin pathway activation and signal transduction
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-01-24 DOI: 10.1038/s41580-024-00823-y
Madelon M. Maurice, Stephane Angers
{"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":"https://doi.org/10.1038/s41580-024-00823-y","url":null,"abstract":"<p>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.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"13 1","pages":""},"PeriodicalIF":112.7,"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}
引用次数: 0
A guide to the biogenesis and functions of endogenous small non-coding RNAs in animals
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-01-24 DOI: 10.1038/s41580-024-00818-9
Karina Jouravleva, Phillip D. Zamore
{"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":"https://doi.org/10.1038/s41580-024-00818-9","url":null,"abstract":"<p>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.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"35 1","pages":""},"PeriodicalIF":112.7,"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}
引用次数: 0
Sequencing technologies to measure translation in single cells 测量单细胞翻译的测序技术
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-01-20 DOI: 10.1038/s41580-024-00822-z
Michael VanInsberghe, Alexander van Oudenaarden
{"title":"Sequencing technologies to measure translation in single cells","authors":"Michael VanInsberghe, Alexander van Oudenaarden","doi":"10.1038/s41580-024-00822-z","DOIUrl":"https://doi.org/10.1038/s41580-024-00822-z","url":null,"abstract":"<p>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.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"7 1","pages":""},"PeriodicalIF":112.7,"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}
引用次数: 0
Proteins that assemble co-translationally lean on their partner for stability 共同翻译组装的蛋白质依靠它们的伙伴来保持稳定性
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-01-07 DOI: 10.1038/s41580-024-00824-x
Kim Baumann
{"title":"Proteins that assemble co-translationally lean on their partner for stability","authors":"Kim Baumann","doi":"10.1038/s41580-024-00824-x","DOIUrl":"https://doi.org/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":"35 1","pages":""},"PeriodicalIF":112.7,"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}
引用次数: 0
Genome characteristics at the borders 边缘的基因组特征
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-01-06 DOI: 10.1038/s41580-024-00819-8
Marina Lusic
{"title":"Genome characteristics at the borders","authors":"Marina Lusic","doi":"10.1038/s41580-024-00819-8","DOIUrl":"https://doi.org/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":"117 1","pages":""},"PeriodicalIF":112.7,"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}
引用次数: 0
Circadian clock communication during homeostasis and ageing 体内平衡和衰老过程中的生物钟通讯
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2025-01-03 DOI: 10.1038/s41580-024-00802-3
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":"https://doi.org/10.1038/s41580-024-00802-3","url":null,"abstract":"<p>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.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"69 1","pages":""},"PeriodicalIF":112.7,"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}
引用次数: 0
The biogenesis and regulation of animal microRNAs 动物microrna的生物发生与调控
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-12-19 DOI: 10.1038/s41580-024-00805-0
Haedong Kim, Young-Yoon Lee, V. Narry Kim
{"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":"https://doi.org/10.1038/s41580-024-00805-0","url":null,"abstract":"<p>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 <i>cis</i>-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.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"31 1","pages":""},"PeriodicalIF":112.7,"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}
引用次数: 0
Modelling human brain development and disease with organoids 用类器官模拟人类大脑发育和疾病
IF 112.7 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-12-12 DOI: 10.1038/s41580-024-00804-1
Marcella Birtele, Madeline Lancaster, Giorgia Quadrato
{"title":"Modelling human brain development and disease with organoids","authors":"Marcella Birtele, Madeline Lancaster, Giorgia Quadrato","doi":"10.1038/s41580-024-00804-1","DOIUrl":"https://doi.org/10.1038/s41580-024-00804-1","url":null,"abstract":"<p>Organoids are systems derived from pluripotent stem cells at the interface between traditional monolayer cultures and in vivo animal models. The structural and functional characteristics of organoids enable the modelling of early stages of brain development in a physiologically relevant 3D environment. Moreover, organoids constitute a tool with which to analyse how individual genetic variation contributes to the susceptibility and progression of neurodevelopmental disorders. This Roadmap article describes the features of brain organoids, focusing on the neocortex, and their advantages and limitations — in comparison with other model systems — for the study of brain development, evolution and disease. We highlight avenues for enhancing the physiological relevance of brain organoids by integrating bioengineering techniques and unbiased high-throughput analyses, and discuss future applications. As organoids advance in mimicking human brain functions, we address the ethical and societal implications of this technology.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"5 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815715","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
Calcium connects lysosomal damage to stress granule formation 钙将溶酶体损伤与应激颗粒形成联系起来
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-12-03 DOI: 10.1038/s41580-024-00817-w
Kim Baumann
{"title":"Calcium connects lysosomal damage to stress granule formation","authors":"Kim Baumann","doi":"10.1038/s41580-024-00817-w","DOIUrl":"10.1038/s41580-024-00817-w","url":null,"abstract":"A calcium-dependent pathway induces stress granule formation and promotes cell survival following lysosomal damage.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"10-10"},"PeriodicalIF":81.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760549","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
m6A ‘encodes’ a dedicated mRNA decay pathway m6A“编码”一个专用的mRNA衰变途径
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-12-03 DOI: 10.1038/s41580-024-00815-y
Eytan Zlotorynski
{"title":"m6A ‘encodes’ a dedicated mRNA decay pathway","authors":"Eytan Zlotorynski","doi":"10.1038/s41580-024-00815-y","DOIUrl":"10.1038/s41580-024-00815-y","url":null,"abstract":"Sites of N6-methyladenosine (m6A) in the coding region of mRNAs can induce a distinct, translation-dependent decay pathway involving mRNA translocation to P-bodies.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"8-8"},"PeriodicalIF":81.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760183","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
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