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The Yin and Yang of replicative aging and rejuvenation 生殖衰老和返老还童的阴阳
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-06-23 DOI: 10.1016/j.gde.2025.102375
Wei-Han Lin , Aliaksandr Damenikan , Yves Barral
{"title":"The Yin and Yang of replicative aging and rejuvenation","authors":"Wei-Han Lin ,&nbsp;Aliaksandr Damenikan ,&nbsp;Yves Barral","doi":"10.1016/j.gde.2025.102375","DOIUrl":"10.1016/j.gde.2025.102375","url":null,"abstract":"<div><div>Budding yeast undergoes replicative aging through asymmetric cell divisions. Yeast mother cells progressively age as they generate successive daughter cells, until they ultimately die. However, their daughters are born rejuvenated, that is, most of them recover a full lifespan potential, with little impact of their mothers’ age at their birth. In this review, we will discuss recent findings regarding the mechanisms of replicative aging and rejuvenation. Based on these insights, we will also discuss which evolutionary forces may have presided over the emergence of aging in yeast. We suggest that aging and rejuvenation represent two adaptive strategies that each bring their own benefits.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102375"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365362","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
Transcriptional adaptation: where mRNA decay meets genetic compensation 转录适应：mRNA衰变与遗传补偿
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-06-10 DOI: 10.1016/j.gde.2025.102369
Lara Falcucci , Brian Juvik , Didier YR Stainier
{"title":"Transcriptional adaptation: where mRNA decay meets genetic compensation","authors":"Lara Falcucci ,&nbsp;Brian Juvik ,&nbsp;Didier YR Stainier","doi":"10.1016/j.gde.2025.102369","DOIUrl":"10.1016/j.gde.2025.102369","url":null,"abstract":"<div><div>Nonsense-mediated mRNA decay (NMD) is a translation-coupled quality control mechanism that safeguards cells against faulty transcripts that could lead to truncated and potentially harmful proteins. However, we posit that there is another side to NMD: it does not just clear away defective transcripts, it also triggers a form of genetic compensation known as transcriptional adaptation (TA). This recently discovered cellular response operates independently of protein loss. Instead, mutant mRNA decay can lead to the upregulation of functional paralogs, thereby compensating for the loss of the mutated gene. Consequently, TA could play a prominent role in genotype-phenotype correlations in human genetic diseases.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102369"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254116","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
NOVA1/2 genes and alternative splicing in neurodevelopment NOVA1/2基因与神经发育中的选择性剪接
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-06-23 DOI: 10.1016/j.gde.2025.102373
Amélie Piton
{"title":"NOVA1/2 genes and alternative splicing in neurodevelopment","authors":"Amélie Piton","doi":"10.1016/j.gde.2025.102373","DOIUrl":"10.1016/j.gde.2025.102373","url":null,"abstract":"<div><div>NOVA1 and NOVA2 are neuron-specific RNA-binding proteins essential for alternative splicing (AS), influencing neurodevelopment by regulating transcript diversity. These proteins recognize YCAY sequences on pre-mRNA, regulating exon inclusion or skipping, intron retention, and alternative polyadenylation. Despite their 75% sequence identity, NOVA1 and NOVA2 exhibit distinct spatiotemporal expression patterns and target specificities, with NOVA2 predominantly expressed in cortical regions and NOVA1 in the cerebellum and spinal cord. <em>De novo</em> truncating variants in <em>NOVA2</em> are responsible for a severe neurodevelopmental disorder (NDD), characterized by intellectual developmental disorder, motor delay, autistic features, and corpus callosum hypoplasia. Loss of <em>Nova2</em> in animal models results in brain development anomalies, such as corpus callosum agenesis in mice, which mirrors the human neurodevelopmental phenotype. If direct evidence remains limited, emerging data suggest that mutations in <em>NOVA1</em> might also be involved in neurological disorders. The contribution of other mRNA-binding proteins to NDD further underscores the critical role of regulation of RNA processing in neurodevelopment. This review explores the diverse functions of NOVA proteins, their impact on AS during brain development, and their implications in brain disorders.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102373"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365363","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
Non-homologous sequence interactions during meiosis: meiotic challenges and evolutionary opportunities 减数分裂过程中的非同源序列相互作用：减数分裂的挑战和进化机会
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-05-23 DOI: 10.1016/j.gde.2025.102365
Beth L Dumont, Mary Ann Handel
{"title":"Non-homologous sequence interactions during meiosis: meiotic challenges and evolutionary opportunities","authors":"Beth L Dumont,&nbsp;Mary Ann Handel","doi":"10.1016/j.gde.2025.102365","DOIUrl":"10.1016/j.gde.2025.102365","url":null,"abstract":"<div><div>A hallmark of meiosis is pairing of homologous chromosomes, an event that ensures proper segregation into the gametes. Homology pairing is crucial to the formation of normal gametes, the maintenance of genomic integrity, and avoidance of aneuploidy. However, chromosomes are not completely homologous. Here we discuss two notable exceptions to homology: the mammalian sex chromosomes and centromeres. In themselves, these exceptions illustrate meiotic adaptations that both ensure correct chromosome segregation and present evolutionary opportunities. More broadly, such examples of non-homology provide a window for viewing normal mechanisms of meiotic pairing and chromosome modifications. Current analyses of mammalian meiotic chromosome dynamics suggest that the basis for the initial recognition of homology early in meiosis may be based in epigenetic chromatin modifications. Chromatin units may both form pairing sites and provide the modifications that allow non-homologous sequences to be tolerated. Despite recent research progress, we have yet to understand why some non-homologies are tolerated, while others lead to aneuploidy. Understanding how genomes evolve strategies to subvert the usual rules of meiosis will benefit from studies focused on the identification and characterization of meiosis in species with recently acquired non-homology. Looking forward, we are now armed with technologies and tools suited to precisely measure the extent of nonhomology across mammalian chromosomes and to probe the molecular and biophysical steps required for the initiation of homologous chromosome recognition and pairing. These goals are important for elucidating an essential mechanism of meiosis and ultimately for advancing the clinical diagnosis of gametic and embryo aneuploidy.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102365"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116256","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
Transposon persistence and control in germ cells 转座子在生殖细胞中的持久性和控制
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-06-18 DOI: 10.1016/j.gde.2025.102370
Lauren Tracy, Zhao Zhang
{"title":"Transposon persistence and control in germ cells","authors":"Lauren Tracy,&nbsp;Zhao Zhang","doi":"10.1016/j.gde.2025.102370","DOIUrl":"10.1016/j.gde.2025.102370","url":null,"abstract":"<div><div>Transposons, or ‘jumping genes’, are ubiquitous genomic elements with the dual capacity to drive evolutionary innovation and disrupt genome integrity through gene mutation and DNA damage. Their activity is particularly significant in germline cells, which transmit genetic material to the next generation. Transposon activity in these cells embodies a delicate balance: while limited transposon activity can introduce genetic diversity and drive evolution, unchecked mobilization risks DNA damage, sterility, and loss of fitness. As ‘selfish genes’, transposons have evolved strategies to ensure their propagation without jeopardizing host survival. This intricate relationship raises compelling questions about how transposon activity is regulated to sustain both genome stability and evolutionary potential. In this review, we explore recent advances in understanding the small RNA pathway that represses transposons in germ cells, the Piwi-interacting RNA pathway. Furthermore, we highlight how transposons creatively bypass repression. These findings illuminate the dynamic interplay between hosts and transposons, offering deeper insights into genome evolution and preservation.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102370"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314499","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
Lineage-specific regulatory evolution: insights from massively parallel reporter assays 谱系特异性调控进化：来自大规模平行报告者分析的见解
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-06-20 DOI: 10.1016/j.gde.2025.102372
Ryder Easterlin , Nadav Ahituv
{"title":"Lineage-specific regulatory evolution: insights from massively parallel reporter assays","authors":"Ryder Easterlin ,&nbsp;Nadav Ahituv","doi":"10.1016/j.gde.2025.102372","DOIUrl":"10.1016/j.gde.2025.102372","url":null,"abstract":"<div><div>Lineage-specific genetic variants play a key role in evolutionary divergence, particularly through changes in <em>cis</em>-regulatory elements that fine-tune gene expression. Massively parallel reporter assays (MPRAs) provide a powerful approach to characterize these variants at scale. This review highlights how MPRAs have been used to study lineage-specific regulatory activity in enhancer elements, including human accelerated regions, human adaptive quickly evolving regions, and short human-specific conserved deletions. We discuss the effects of enhancer variation on traits distinguishing modern humans, archaic hominins, and primates, as well as how MPRAs disentangle <em>cis</em>- and <em>trans</em>-regulatory contributions to gene expression divergence. As MPRA technology advances, integrating it with CRISPR-based validation and artificial intelligence–driven predictions will further illuminate the role of lineage-specific regulatory evolution.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102372"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331473","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
Paternal effects on telomere integrity during the sperm-to-embryo transition 精子到胚胎转变过程中，父系对端粒完整性的影响
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-04-25 DOI: 10.1016/j.gde.2025.102348
Sung-Ya Lin , Mia T Levine
{"title":"Paternal effects on telomere integrity during the sperm-to-embryo transition","authors":"Sung-Ya Lin ,&nbsp;Mia T Levine","doi":"10.1016/j.gde.2025.102348","DOIUrl":"10.1016/j.gde.2025.102348","url":null,"abstract":"<div><div>Telomeres are essential nucleoprotein structures that preserve our terminal DNA sequence and protect chromosome ends from fusion. Our vast knowledge of telomeres comes almost entirely from studies of healthy and diseased somatic cells. However, building evidence suggests that the molecules and mechanisms required for telomere integrity in somatic cells are insufficient to preserve telomere integrity during the sperm-to-embryo transition. Here, we review this growing body of work on telomere ‘paternal effects’, wherein zygotic telomere integrity is determined not by the genotype of the zygote but instead by the genotype of the father. Direct inheritance of sperm-specific proteins establishes paternal telomere epigenetic identity, while direct inheritance of sperm telomere length contributes to telomere length inheritance. Together, these investigations of telomere integrity through the sperm-to-embryo transition reveal potent paternal effects on zygotic telomere functions, with implications for human infertility.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102348"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868698","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
From conservation to adaptation: understanding the synaptonemal complex’s evolutionary dynamics 从保守到适应：理解突触复合体的进化动力学
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-04-16 DOI: 10.1016/j.gde.2025.102349
Stefanie Williams, Robin Scott Hawley
{"title":"From conservation to adaptation: understanding the synaptonemal complex’s evolutionary dynamics","authors":"Stefanie Williams,&nbsp;Robin Scott Hawley","doi":"10.1016/j.gde.2025.102349","DOIUrl":"10.1016/j.gde.2025.102349","url":null,"abstract":"<div><div>The synaptonemal complex (SC) is structurally conserved across eukaryotes and is essential for a proper progression of meiosis. Despite this conservation, SC protein sequences diverge drastically. In this review, we explore findings on SC protein evolution, highlighting key differences and commonalities among lineages like the <em>Caenorhabditis</em> and the <em>Drosophila</em> genera. We further explore known cases where the SC and its proteins adopt novel functional roles and discuss why knowledge of these cases could be important for the study of canonical SC biology. The existing studies demonstrate that work on the evolutionary biology of SC proteins and functional studies in more diverse meiotic research organisms should play a major role in aiding our understanding of SC structure and functions.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102349"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843881","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
Spliceosome complex and neurodevelopmental disorders 剪接体复合体与神经发育障碍
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-05-15 DOI: 10.1016/j.gde.2025.102358
Hannah M Deutsch , Yuanquan Song , Dong Li
{"title":"Spliceosome complex and neurodevelopmental disorders","authors":"Hannah M Deutsch ,&nbsp;Yuanquan Song ,&nbsp;Dong Li","doi":"10.1016/j.gde.2025.102358","DOIUrl":"10.1016/j.gde.2025.102358","url":null,"abstract":"<div><div>Neurodevelopment requires complex spatiotemporal expression, which heavily relies on proper RNA splicing. The spliceosome is a ribonucleoprotein complex that removes introns from pre-mRNA, joins exons, and produces mature mRNA. Pathogenic variants in genes that code for spliceosome RNAs and proteins cause RNA mis-splicing and spliceosomopathies. Splicing defects during nervous system development upend the tightly controlled neurodevelopmental process, leading to neurodevelopmental disorders (NDDs). Despite the fact that the spliceosome is expressed in every cell, not all spliceosomopathies present as NDDs; spliceosomopathies are often tissue-specific in that a variant has a greater impact on certain cell lineages or cell types. Here we discuss spliceosomopathies whose presentations include NDDs and focus on spliceosome-coding genes.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102358"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069178","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: Emerging perspectives in genome architecture and gene regulation 编辑概述：基因组结构和基因调控的新兴观点
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-08-01 Epub Date: 2025-05-12 DOI: 10.1016/j.gde.2025.102355
Marcelo Nollmann , Anders S. Hansen
{"title":"Editorial overview: Emerging perspectives in genome architecture and gene regulation","authors":"Marcelo Nollmann ,&nbsp;Anders S. Hansen","doi":"10.1016/j.gde.2025.102355","DOIUrl":"10.1016/j.gde.2025.102355","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102355"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143934880","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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