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Unlocking regeneration: how partial reprogramming resembles tissue healing 解锁再生：部分重编程如何类似于组织愈合
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-04-30 DOI: 10.1016/j.gde.2025.102351
Melissa T Adams, Heinrich Jasper, Lluc Mosteiro
{"title":"Unlocking regeneration: how partial reprogramming resembles tissue healing","authors":"Melissa T Adams,&nbsp;Heinrich Jasper,&nbsp;Lluc Mosteiro","doi":"10.1016/j.gde.2025.102351","DOIUrl":"10.1016/j.gde.2025.102351","url":null,"abstract":"<div><div>Partial reprogramming achieved by the transient expression of the transcription factors (TFs) Oct4, Sox2, Klf4 and C-Myc (abbreviated OSKM) can erase aging and damage features in cells, leading to increased healthspan, lifespan and tissue regeneration. Recent reports suggest that the mechanisms of partial reprogramming may share some similarities with natural dedifferentiation and regeneration. Both processes appear to involve the transient repression of somatic identity through the sequestration of somatic identity TFs to noncanonical sites, which are opened by the high expression of pioneer TFs, leading to transient dedifferentiation into a fetal-like state. Here, we review the reported benefits of partial reprogramming on tissue regeneration and propose a common mechanism of epigenetic remodeling with natural regeneration after tissue injury.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102351"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890916","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
Interplay of transposable elements and ageing: epigenetic regulation and potential epitranscriptomic influence 转座因子与衰老的相互作用：表观遗传调控和潜在的表转录组影响
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-06-01 Epub Date: 2025-03-17 DOI: 10.1016/j.gde.2025.102331
Raquel García-Vílchez, Diana Guallar
{"title":"Interplay of transposable elements and ageing: epigenetic regulation and potential epitranscriptomic influence","authors":"Raquel García-Vílchez,&nbsp;Diana Guallar","doi":"10.1016/j.gde.2025.102331","DOIUrl":"10.1016/j.gde.2025.102331","url":null,"abstract":"<div><div>Transposable elements (TEs) are mobile elements, which have been crucial for mammalian genome evolution and function. Their activity, which influences genomic stability, gene expression and chromatin state, is tightly regulated by complex mechanisms. This review examines recent findings on TE regulation and the dynamics and connection during the ageing process. Here, we explore the interplay between chromatin state, DNA, RNA, and histone modifications in controlling TE activity, with a special emphasis in elucidating the emerging role of epitranscriptomic modifications in TE regulation. Additionally, we analyse the connection between TE activation and ageing, with the perspective for future research that could reveal novel targets for alleviating physiological and pathological ageing and age-related diseases.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102331"},"PeriodicalIF":3.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632024","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
Alternative splicing in addiction 成瘾中的选择性剪接
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-06-01 Epub Date: 2025-03-19 DOI: 10.1016/j.gde.2025.102340
Akanksha Bhatnagar , Elizabeth A Heller
{"title":"Alternative splicing in addiction","authors":"Akanksha Bhatnagar ,&nbsp;Elizabeth A Heller","doi":"10.1016/j.gde.2025.102340","DOIUrl":"10.1016/j.gde.2025.102340","url":null,"abstract":"<div><div>Addiction is a chronic and relapsing medical condition characterized by the compulsive use of drugs or alcohol despite harmful consequences. While transcriptional regulation has long been recognized for its role in addiction, recent genome-wide analyses have uncovered widespread alternative splicing changes that shift protein isoform diversity in multiple brain reward regions central to addiction. In this review, we discuss emerging research and evidence that alternative splicing is dysregulated in cocaine, alcohol, and opioid use disorders.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102340"},"PeriodicalIF":3.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644512","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
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 : 2025-06-01 Epub 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":"2025-06-01","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
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 : 2025-06-01 Epub 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":"2025-06-01","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
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 : 2025-06-01 Epub 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":"2025-06-01","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
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 : 2025-06-01 Epub 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":"2025-06-01","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
No more nonsense: evaluating poison exons as therapeutic targets in neurodevelopmental disorders 没有更多的废话：评估毒性外显子作为神经发育障碍的治疗靶点
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-06-01 Epub Date: 2025-04-09 DOI: 10.1016/j.gde.2025.102346
Shreeya Bakshi, Lori L Isom
{"title":"No more nonsense: evaluating poison exons as therapeutic targets in neurodevelopmental disorders","authors":"Shreeya Bakshi,&nbsp;Lori L Isom","doi":"10.1016/j.gde.2025.102346","DOIUrl":"10.1016/j.gde.2025.102346","url":null,"abstract":"<div><div>Alternative splicing of pre-mRNA generates multiple transcripts from a single gene, contributing to transcriptomic diversity. Alternative splicing can result in inclusion of poison exons (PEs), which contain a premature stop codons (PTC) that target transcripts for nonsense-mediated decay (NMD). PE-containing transcripts are prevalent in the brain, where they can play roles in fine-tuning mRNA and protein levels. Antisense, or splice-switching, oligonucleotides (ASOs/SSOs) are used to target PEs to reduce their inclusion and treat neurodevelopmental disorders. ASOs/SSOs address the genetic causes of disease and are precision therapies that can provide a cure rather than only address disease symptoms. This review explores the role of PEs in the brain, therapeutic targeting of PEs, and current challenges in our understanding of PEs.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102346"},"PeriodicalIF":3.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799968","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
Genomic snowflakes: how the uniqueness of DNA folding allows us to smell the chemical universe 基因组雪花：DNA折叠的独特性如何让我们闻到化学宇宙
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-06-01 Epub Date: 2025-03-18 DOI: 10.1016/j.gde.2025.102329
Longzhi Tan , X. Sunney Xie , Stavros Lomvardas
{"title":"Genomic snowflakes: how the uniqueness of DNA folding allows us to smell the chemical universe","authors":"Longzhi Tan ,&nbsp;X. Sunney Xie ,&nbsp;Stavros Lomvardas","doi":"10.1016/j.gde.2025.102329","DOIUrl":"10.1016/j.gde.2025.102329","url":null,"abstract":"<div><div>Olfactory receptor (OR) gene choice, the stable expression of one out of &gt;2000 OR alleles by olfactory sensory neurons, constitutes a gene regulatory process that is driven by three-dimensional nuclear architecture. Moreover, the differentiation-dependent process that culminates in monogenic and monoallelic OR transcription represents a powerful demonstration of the rich mechanistic insight that single-cell genomics and multiomics can provide toward the understanding of a biological process. At this review, we describe the latest advances in the understanding of OR gene regulation and highlight important standing questions regarding the emerging specificity of ultra-long-range genomic interaction and the contribution of transcription and noncoding RNAs.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102329"},"PeriodicalIF":3.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642733","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
Recent advances in RNA-based therapeutics for neurodevelopmental disorders 基于rna的神经发育障碍治疗的最新进展
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-06-01 Epub Date: 2025-03-21 DOI: 10.1016/j.gde.2025.102339
Harini P Tirumala , Huda Y Zoghbi
{"title":"Recent advances in RNA-based therapeutics for neurodevelopmental disorders","authors":"Harini P Tirumala ,&nbsp;Huda Y Zoghbi","doi":"10.1016/j.gde.2025.102339","DOIUrl":"10.1016/j.gde.2025.102339","url":null,"abstract":"<div><div>A significant proportion of neurodevelopmental disorders (NDDs) are caused by gain-of-function (GOF) or loss-of-function (LOF) of specific genes. Strategies to normalize disease gene expression offer therapeutic potential for these disorders. The success and approval of RNA-based therapeutics for various disorders have led to a surge in RNA-based therapeutic research for NDDs with antisense oligonucleotides leading the field. This review discusses recent advances in therapeutic strategies that target pre-mRNA or mRNA for GOF and LOF NDDs that have promising preclinical evidence. These developments highlight important considerations and exciting future avenues for the development of therapies for NDDs.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102339"},"PeriodicalIF":3.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679141","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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