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Current Opinion in Genetics & Development最新文献

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Reshaping transcription and translation dynamics during the awakening of the zygotic genome 在合子基因组觉醒期间重塑转录和翻译动力学
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-04-05 DOI: 10.1016/j.gde.2025.102344
Louise Maillard , Pierre Bensidoun , Mounia Lagha
{"title":"Reshaping transcription and translation dynamics during the awakening of the zygotic genome","authors":"Louise Maillard ,&nbsp;Pierre Bensidoun ,&nbsp;Mounia Lagha","doi":"10.1016/j.gde.2025.102344","DOIUrl":"10.1016/j.gde.2025.102344","url":null,"abstract":"<div><div>During the oocyte-to-embryo transition, the transcriptome and proteome are dramatically reshaped. This transition entails a shift from maternally inherited mRNAs to newly synthesized transcripts, produced during the zygotic genome activation (ZGA). Furthermore, a crucial transcription and translation selectivity is required for early embryonic development. Studies across various model organisms have revealed conserved <em>cis-</em> and <em>trans-</em>regulatory mechanisms dictating the regimes by which mRNA and proteins are produced during this critical phase. In this article, we highlight recent technological and conceptual advances that deepen our understanding of how the tuning of both transcription and translation evolves during ZGA.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102344"},"PeriodicalIF":3.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776585","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
To splice or not to splice: pseudoexons in neurological disease and opportunities for intervention 剪接或不剪接：神经系统疾病中的假外显子及其干预机会
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-03-29 DOI: 10.1016/j.gde.2025.102343
Sue Fletcher , Niall P Keegan , Rita Mejzini , Ianthe L Pitout
{"title":"To splice or not to splice: pseudoexons in neurological disease and opportunities for intervention","authors":"Sue Fletcher ,&nbsp;Niall P Keegan ,&nbsp;Rita Mejzini ,&nbsp;Ianthe L Pitout","doi":"10.1016/j.gde.2025.102343","DOIUrl":"10.1016/j.gde.2025.102343","url":null,"abstract":"<div><div>Accurate exon selection and processing of pre-messenger RNA are crucial for normal gene expression. Mutations that alter splicing disrupt pre-mRNA processing and can have diverse effects on transcript structure, making the consequences of many such mutations difficult to predict. While next-generation sequencing technologies have transformed genetic diagnosis for many patients, deep intronic variants generally evade detection and characterisation. Of all the known types of splicing mutations, the most elusive to predict are those that activate pseudoexons. Because transcripts that contain pseudoexons are otherwise generally intact, exclusion (or ‘skipping’) of the pseudoexon during processing of the pre-mRNA is likely to generate a normal, functional mRNA. Characterisation of pseudoexon mutations will open opportunities for the development of antisense oligonucleotide strategies to overcome these disease-causing mutations.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102343"},"PeriodicalIF":3.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734631","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
The human endometrium: atlases, models, and prospects 人类子宫内膜：地图集、模型和前景
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-03-27 DOI: 10.1016/j.gde.2025.102341
Frederick CK Wong , Christina E Kim , Luz Garcia-Alonso , Roser Vento-Tormo
{"title":"The human endometrium: atlases, models, and prospects","authors":"Frederick CK Wong ,&nbsp;Christina E Kim ,&nbsp;Luz Garcia-Alonso ,&nbsp;Roser Vento-Tormo","doi":"10.1016/j.gde.2025.102341","DOIUrl":"10.1016/j.gde.2025.102341","url":null,"abstract":"<div><div>Approximately every month, the human endometrium undergoes a cycle of proliferation, differentiation, and, in the absence of pregnancy, shedding and repair. Each cycle relies on intricate interorgan coordination of hormonal secretions. Endometrial dysfunction causes significant health complications, including abnormal menstrual bleeding and endometriosis. However, effective diagnosis and treatments are hampered by understudied aetiology. Recent single-cell profiling has disentangled the diverse and dynamic nature of the endometrium, revealing regulatory roles of WNT, NOTCH, and TGF<em>β</em> signalling. These insights have informed mechanistic studies enabled by advanced <em>in vitro</em> models that capture endometrial cellular heterogeneity and structure. In this review, we outline key single-cell transcriptomics atlases and models that provided new avenues for studying endometrial biology, discuss their limitations, and propose future directions.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102341"},"PeriodicalIF":3.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705922","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 : 2025-03-21 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":"2025-03-21","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
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 : 2025-03-19 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":"2025-03-19","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
Totipotency or plenipotency: rethinking stem cell bipotentiality 全能性或全能性：重新思考干细胞的双潜能性
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-03-19 DOI: 10.1016/j.gde.2025.102342
Duancheng Wen , Jianlong Wang
{"title":"Totipotency or plenipotency: rethinking stem cell bipotentiality","authors":"Duancheng Wen ,&nbsp;Jianlong Wang","doi":"10.1016/j.gde.2025.102342","DOIUrl":"10.1016/j.gde.2025.102342","url":null,"abstract":"<div><div>The term ‘totipotency’ has often been misapplied in stem cell research to describe cells with embryonic and extraembryonic bipotentiality, despite a lack of evidence that they can generate an entire organism from a single cell. Additionally, no specific term currently distinguishes bipotential stem cells from pluripotent cells, which contribute poorly to extraembryonic tissues. This review examines the developmental continuum from totipotency to pluripotency in early embryos and revisits the previously proposed concept of plenipotency in preimplantation development. We evaluate emerging stem cell models that exhibit bipotentiality but have lost the ability to autonomously initiate and sustain the sequential fate decisions necessary to develop into a complete organism. Unlike totipotent embryonic cells, which retain the information required to initiate fate decisions at the correct timing and cell numbers, these stem cells have lost that capacity. This loss of critical developmental information distinguishes totipotency from plenipotency, with bipotential stem cells aligning more closely with the latter. By distinguishing plenipotency from totipotency and pluripotency, we aim to refine terminology, enhance our understanding of early embryonic development, and address ethical considerations in human research.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102342"},"PeriodicalIF":3.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644513","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 : 2025-03-18 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":"2025-03-18","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
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 : 2025-03-17 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":"2025-03-17","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
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
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