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Modification of the RNA methylome in neurodevelopmental disorders 神经发育障碍中RNA甲基组的修饰
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-03-12 DOI: 10.1016/j.gde.2025.102330
Adriana PerezGrovas-Saltijeral, Joseph Stones, Oliver C Orji, Hala Shaker, Helen M Knight
{"title":"Modification of the RNA methylome in neurodevelopmental disorders","authors":"Adriana PerezGrovas-Saltijeral,&nbsp;Joseph Stones,&nbsp;Oliver C Orji,&nbsp;Hala Shaker,&nbsp;Helen M Knight","doi":"10.1016/j.gde.2025.102330","DOIUrl":"10.1016/j.gde.2025.102330","url":null,"abstract":"<div><div>RNA metabolism is fundamental to protein synthesis, degradation and transport of molecules. Methylation of RNA influences the processing of mRNA, noncoding RNA, tRNA and rRNA. Here, we review accumulating evidence that disruption to the RNA methylome impairs developmental processes and causes neurodevelopmental conditions. We first describe mutated RNA methylation effector protein genes that give rise to neurodevelopmental syndromes. We consider the biological processes thereby disrupted, including translational dynamics at cytoplasmic and mt-ribosomes, synaptic function, energy production and cellular stress. Finally, we discuss novel forms of methylated RNA, such as R-loops and circular RNAs, which may contribute to disease processes. These findings herald an exciting new era to brain research and highlight the significant potential of manipulating the RNA methylome as a therapeutic target in the treatment of neurodevelopmental disorders.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102330"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bridging spatial and temporal scales of developmental gene regulation 连接发育基因调控的时空尺度
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-03-12 DOI: 10.1016/j.gde.2025.102328
Andrés H Cardona , Márcia M Peixoto , Tohn Borjigin , Thomas Gregor
{"title":"Bridging spatial and temporal scales of developmental gene regulation","authors":"Andrés H Cardona ,&nbsp;Márcia M Peixoto ,&nbsp;Tohn Borjigin ,&nbsp;Thomas Gregor","doi":"10.1016/j.gde.2025.102328","DOIUrl":"10.1016/j.gde.2025.102328","url":null,"abstract":"<div><div>The development of multicellular organisms relies on the precise coordination of molecular events across multiple spatial and temporal scales. Understanding how information flows from molecular interactions to cellular processes and tissue organization during development is crucial for explaining the remarkable reproducibility of complex organisms. This review explores how chromatin-encoded information is transduced from localized transcriptional events to global gene expression patterns, highlighting the challenge of bridging these scales. We discuss recent experimental findings and theoretical frameworks, emphasizing polymer physics as a tool for describing the relationship between chromatin structure and dynamics across scales. By integrating these perspectives, we aim to clarify how gene regulation is coordinated across levels of biological organization and suggest strategies for future experimental approaches.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102328"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multi-organelle-mediated mRNA localization in neurons and links to disease 神经元中多细胞器介导的mRNA定位及其与疾病的联系
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-03-07 DOI: 10.1016/j.gde.2025.102332
Vivienne Aline Bauer, Koppers Max
{"title":"Multi-organelle-mediated mRNA localization in neurons and links to disease","authors":"Vivienne Aline Bauer,&nbsp;Koppers Max","doi":"10.1016/j.gde.2025.102332","DOIUrl":"10.1016/j.gde.2025.102332","url":null,"abstract":"<div><div>Brain function requires precise spatiotemporal regulation of the neuronal proteome. To allow adaptation of the proteome in distal outposts of neurons, mRNAs are transported into neurites for localized translation. This mRNA localization and local translation is crucial for neuron function and maintenance, and dysregulation of these processes can contribute to neurological disease. Recently, organelles have emerged as key players in regulating mRNA localization and local translation in dendrites and axons. In this review, we discuss the current evidence and open questions for this organelle-mediated mRNA localization. We highlight an emerging model in which multiple organelles create and orchestrate a subcellular microenvironment that can support precise mRNA localization and selective translation. This seems essential for maintaining organellar and neuronal function and health, as mutations in many of the involved proteins lead to various neurological disorders.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102332"},"PeriodicalIF":3.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pluripotent stem cell–derived mesenchymal stem cells for therapeutic applications, developmental study, and cancer research 多能干细胞衍生的间充质干细胞用于治疗应用、发育研究和癌症研究
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-03-06 DOI: 10.1016/j.gde.2025.102327
Siyi Fu, Cheung K Yeung, Ren-He Xu
{"title":"Pluripotent stem cell–derived mesenchymal stem cells for therapeutic applications, developmental study, and cancer research","authors":"Siyi Fu,&nbsp;Cheung K Yeung,&nbsp;Ren-He Xu","doi":"10.1016/j.gde.2025.102327","DOIUrl":"10.1016/j.gde.2025.102327","url":null,"abstract":"<div><div>Human mesenchymal stem cells (MSCs) have been widely studied and applied for the treatment of various diseases due to their crucial role in tissue repair and regeneration. Compared to MSCs isolated from somatic tissues, MSCs differentiated from human pluripotent stem cells (ps-MSCs) have demonstrated similar therapeutic effects while possessing some advantages in quality control and assurance, given their unlimited and consistent supply of source cells. This makes ps-MSCs highly druggable and promising for therapeutic applications. In this minireview, we introduce the latest progress in ps-MSC research, focusing on the therapeutic properties, origin, <em>in vivo</em> development, and application of ps-MSCs in cancer research. We will also discuss the perspectives and challenges of this relatively new source of MSCs.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102327"},"PeriodicalIF":3.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
R-loop homeostasis in genome dynamics, gene expression and development 基因组动力学、基因表达和发育中的r环稳态
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-03-04 DOI: 10.1016/j.gde.2025.102325
Paula Aguilera , Andrés Aguilera
{"title":"R-loop homeostasis in genome dynamics, gene expression and development","authors":"Paula Aguilera ,&nbsp;Andrés Aguilera","doi":"10.1016/j.gde.2025.102325","DOIUrl":"10.1016/j.gde.2025.102325","url":null,"abstract":"<div><div>R-loops are double-edge swords with functional roles that in many cases constitute a threat to genome integrity and gene expression with relevant consequences in cell physiology and development. A number of factors have evolved to control R-loop homeostasis by acting at the levels of R-loop prevention, resolution, or the repair of the R-loop-induced DNA lesion. Deciphering the role of R-loops generated under different stresses and the plethora of processes controlling their homeostasis has become crucial to evaluate their impact in cell physiology and the biological significance of their association with development and disease. Here, we review publications of the last 2 years that help understand their biological role.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102325"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Editorial overview: Peering into our history through a genetic lens: How advances in genetics are changing our understanding of human evolution 编辑概述：通过基因镜头窥视我们的历史：遗传学的进步如何改变我们对人类进化的理解
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-02-24 DOI: 10.1016/j.gde.2025.102326
Jason L Stein , Alex A Pollen
{"title":"Editorial overview: Peering into our history through a genetic lens: How advances in genetics are changing our understanding of human evolution","authors":"Jason L Stein ,&nbsp;Alex A Pollen","doi":"10.1016/j.gde.2025.102326","DOIUrl":"10.1016/j.gde.2025.102326","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102326"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Modeling forebrain regional development and connectivity by human brain organoids 用人脑类器官模拟前脑区域发育和连通性
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-02-20 DOI: 10.1016/j.gde.2025.102324
Mu Seog Choe , Cynthia Lo , In-Hyun Park
{"title":"Modeling forebrain regional development and connectivity by human brain organoids","authors":"Mu Seog Choe ,&nbsp;Cynthia Lo ,&nbsp;In-Hyun Park","doi":"10.1016/j.gde.2025.102324","DOIUrl":"10.1016/j.gde.2025.102324","url":null,"abstract":"<div><div>The forebrain is one of the most important brain structures for modern human existence, which houses the uniquely sophisticated social and cognitive functions that distinguish our species. Therefore, modeling the forebrain development by using human cells is especially critical for our understanding of the intricacies of human development and devising treatments for related diseases. Recent advancements in brain organoid fields have offered unprecedented tools to investigate forebrain development from studies on specific regions to exploring tract formation and connectivity between different regions of the forebrain. In this review, we discuss the developmental biology of the forebrain and diverse methods for modeling its development by using organoids.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102324"},"PeriodicalIF":3.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Principles of long-range gene regulation 远程基因调控原理
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-02-13 DOI: 10.1016/j.gde.2025.102323
Sanyami Zunjarrao, Maria Cristina Gambetta
{"title":"Principles of long-range gene regulation","authors":"Sanyami Zunjarrao,&nbsp;Maria Cristina Gambetta","doi":"10.1016/j.gde.2025.102323","DOIUrl":"10.1016/j.gde.2025.102323","url":null,"abstract":"<div><div>Transcription from gene promoters occurs in specific spatiotemporal patterns in multicellular organisms, controlled by genomic regulatory elements. The communication between a regulatory element and a promoter requires a certain degree of physical proximity between them; hence, most gene regulation occurs locally in the genome. However, recent discoveries have revealed long-range gene regulation strategies that enhance interactions between regulatory elements and promoters by overcoming the distances between them in the linear genome. These new findings challenge the traditional view of how gene expression patterns are controlled. This review examines long-range gene regulation strategies recently reported in Drosophila and mammals, offering insights into their mechanisms and evolution.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102323"},"PeriodicalIF":3.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the connection between RNA splicing and intellectual disability 探索RNA剪接与智力缺陷之间的联系
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-02-08 DOI: 10.1016/j.gde.2025.102322
Anthony Caputo, Ashleigh E Schaffer
{"title":"Exploring the connection between RNA splicing and intellectual disability","authors":"Anthony Caputo,&nbsp;Ashleigh E Schaffer","doi":"10.1016/j.gde.2025.102322","DOIUrl":"10.1016/j.gde.2025.102322","url":null,"abstract":"<div><div>Intellectual disability (ID) is a broad diagnostic category that encompasses individuals with impaired cognitive ability. While these disorders have heterogeneous causes, recent developments in next-generation sequencing (NGS) are revealing the prevalence of genetic etiologies. In particular, germline mutations in genes that affect RNA splicing are increasingly common causes of ID disorders. Research to elucidate the functional relationship between splicing and neurodevelopment is critical since molecular therapeutics require a nuanced understanding of the pathological mechanism. In this review, we first summarize the trends that have led to the discovery of the RNA splicing–ID relationship, then discuss recent progress and future directions for research surrounding RNA splicing in neurodevelopment. Finally, we speak on how these results may serve as the foundation for burgeoning therapies.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102322"},"PeriodicalIF":3.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Decoding N6-methyladenosine’s dynamic role in stem cell fate and early embryo development: insights into RNA–chromatin interactions 解码n6 -甲基腺苷在干细胞命运和早期胚胎发育中的动态作用：rna -染色质相互作用的见解
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-02-04 DOI: 10.1016/j.gde.2025.102311
Lei Yang , Mingli Ma , Yawei Gao , Jun Liu
{"title":"Decoding N6-methyladenosine’s dynamic role in stem cell fate and early embryo development: insights into RNA–chromatin interactions","authors":"Lei Yang ,&nbsp;Mingli Ma ,&nbsp;Yawei Gao ,&nbsp;Jun Liu","doi":"10.1016/j.gde.2025.102311","DOIUrl":"10.1016/j.gde.2025.102311","url":null,"abstract":"<div><div><em>N</em><sup>6</sup>-methyladenosine (m<sup>6</sup>A), a reversible and dynamic RNA modification, plays pivotal roles in regulating stem cell pluripotency and early embryogenesis. Disruptions in m<sup>6</sup>A homeostasis lead to profound developmental defects, impairing processes such as stem cell self-renewal, lineage specification, oocyte maturation, zygotic genome activation, and maternal RNA degradation after fertilization. Beyond its well-recognized roles in mRNA transport, stability, and translation, recent studies have highlighted m<sup>6</sup>A’s critical role in transcriptional regulation through intricate RNA–chromatin interactions, notably involving chromatin-associated regulatory RNAs (carRNAs) and retrotransposon RNAs. This review delves into the dynamic regulatory landscape of m<sup>6</sup>A, highlighting its critical interplay with chromatin modifications, and explores its broader implications in stem cell biology and early embryonic development.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102311"},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143168794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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