Pub Date : 2024-07-23DOI: 10.1016/j.tcb.2024.06.008
Vivian Kalamara, George A Garinis
Genomic instability poses a formidable threat to cellular vitality and wellbeing, prompting cells to deploy an intricate DNA damage response (DDR) mechanism. Recent evidence has suggested that RNA is intricately linked to the DDR by serving as template, scaffold, or regulator during the repair of DNA damage. Additionally, RNA molecules undergo modifications, contributing to the epitranscriptome, a dynamic regulatory layer influencing cellular responses to genotoxic stress. The intricate interplay between RNA and the DDR sheds new light on how the RNA epigenome contributes to the maintenance of genomic integrity and ultimately shapes the fate of damaged cells.
基因组的不稳定性对细胞的活力和健康构成了巨大威胁,促使细胞部署复杂的 DNA 损伤应答(DDR)机制。最近的证据表明,RNA 在 DNA 损伤修复过程中充当模板、支架或调节器的角色,与 DDR 密切相关。此外,RNA 分子会发生修饰,从而形成表转录组(epitranscriptome),这是一个影响细胞对基因毒性应激反应的动态调控层。RNA 与 DDR 之间错综复杂的相互作用为我们揭示了 RNA 表观基因组如何有助于维持基因组完整性并最终决定受损细胞的命运。
{"title":"The epitranscriptome: reshaping the DNA damage response.","authors":"Vivian Kalamara, George A Garinis","doi":"10.1016/j.tcb.2024.06.008","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.06.008","url":null,"abstract":"<p><p>Genomic instability poses a formidable threat to cellular vitality and wellbeing, prompting cells to deploy an intricate DNA damage response (DDR) mechanism. Recent evidence has suggested that RNA is intricately linked to the DDR by serving as template, scaffold, or regulator during the repair of DNA damage. Additionally, RNA molecules undergo modifications, contributing to the epitranscriptome, a dynamic regulatory layer influencing cellular responses to genotoxic stress. The intricate interplay between RNA and the DDR sheds new light on how the RNA epigenome contributes to the maintenance of genomic integrity and ultimately shapes the fate of damaged cells.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762962","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}
Pub Date : 2024-07-18DOI: 10.1016/j.tcb.2024.06.006
Jan Rehwinkel, Parinaz Mehdipour
Adenosine deaminase acting on RNA 1 (ADAR1) converts adenosine to inosine in double-stranded RNA (dsRNA) molecules, a process known as A-to-I editing. ADAR1 deficiency in humans and mice results in profound inflammatory diseases characterised by the spontaneous induction of innate immunity. In cells lacking ADAR1, unedited RNAs activate RNA sensors. These include melanoma differentiation-associated gene 5 (MDA5) that induces the expression of cytokines, particularly type I interferons (IFNs), protein kinase R (PKR), oligoadenylate synthase (OAS), and Z-DNA/RNA binding protein 1 (ZBP1). Immunogenic RNAs 'defused' by ADAR1 may include transcripts from repetitive elements and other long duplex RNAs. Here, we review these recent fundamental discoveries and discuss implications for human diseases. Some tumours depend on ADAR1 to escape immune surveillance, opening the possibility of unleashing anticancer therapies with ADAR1 inhibitors.
{"title":"ADAR1: from basic mechanisms to inhibitors.","authors":"Jan Rehwinkel, Parinaz Mehdipour","doi":"10.1016/j.tcb.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.06.006","url":null,"abstract":"<p><p>Adenosine deaminase acting on RNA 1 (ADAR1) converts adenosine to inosine in double-stranded RNA (dsRNA) molecules, a process known as A-to-I editing. ADAR1 deficiency in humans and mice results in profound inflammatory diseases characterised by the spontaneous induction of innate immunity. In cells lacking ADAR1, unedited RNAs activate RNA sensors. These include melanoma differentiation-associated gene 5 (MDA5) that induces the expression of cytokines, particularly type I interferons (IFNs), protein kinase R (PKR), oligoadenylate synthase (OAS), and Z-DNA/RNA binding protein 1 (ZBP1). Immunogenic RNAs 'defused' by ADAR1 may include transcripts from repetitive elements and other long duplex RNAs. Here, we review these recent fundamental discoveries and discuss implications for human diseases. Some tumours depend on ADAR1 to escape immune surveillance, opening the possibility of unleashing anticancer therapies with ADAR1 inhibitors.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728381","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}
Pub Date : 2024-07-17DOI: 10.1016/j.tcb.2024.06.007
Several lines of evidence suggest that the age-dependent accumulation of senescent cells leads to chronic tissue microinflammation, which in turn contributes to age-related pathologies. In general, senescent cells can be eliminated by the host’s innate and adaptive immune surveillance system, including macrophages, NK cells, and T cells. Impaired immune surveillance leads to the accumulation of senescent cells and accelerates the aging process. Recently, senescent cells, like cancer cells, have been shown to express certain types of immune checkpoint proteins as well as non-classical immune-tolerant MHC variants, leading to immune escape from surveillance systems. Thus, immune checkpoint blockade (ICB) may be a promising strategy to enhance immune surveillance of senescence, leading to the amelioration of some age-related diseases and tissue dysfunction.
多种证据表明,衰老细胞的积累与年龄有关,会导致慢性组织微炎症,进而引发与年龄有关的病症。一般来说,衰老细胞可被宿主的先天性和适应性免疫监视系统(包括巨噬细胞、NK 细胞和 T 细胞)清除。免疫监视功能受损会导致衰老细胞的积累并加速衰老过程。最近的研究表明,衰老细胞和癌细胞一样,会表达某些类型的免疫检查点蛋白以及非经典的免疫耐受 MHC 变异体,从而导致免疫逃逸监视系统。因此,免疫检查点阻断(ICB)可能是一种很有前景的策略,可加强对衰老的免疫监视,从而改善一些与年龄有关的疾病和组织功能障碍。
{"title":"Immune surveillance of senescence: potential application to age-related diseases","authors":"","doi":"10.1016/j.tcb.2024.06.007","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.06.007","url":null,"abstract":"<p>Several lines of evidence suggest that the age-dependent accumulation of senescent cells leads to chronic tissue microinflammation, which in turn contributes to age-related pathologies. In general, senescent cells can be eliminated by the host’s innate and adaptive immune surveillance system, including macrophages, NK cells, and T cells. Impaired immune surveillance leads to the accumulation of senescent cells and accelerates the aging process. Recently, senescent cells, like cancer cells, have been shown to express certain types of immune checkpoint proteins as well as non-classical immune-tolerant MHC variants, leading to immune escape from surveillance systems. Thus, immune checkpoint blockade (ICB) may be a promising strategy to enhance immune surveillance of senescence, leading to the amelioration of some age-related diseases and tissue dysfunction.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":null,"pages":null},"PeriodicalIF":19.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141718236","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}
Pub Date : 2024-07-05DOI: 10.1016/s0962-8924(24)00125-9
No Abstract
无摘要
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/s0962-8924(24)00125-9","DOIUrl":"https://doi.org/10.1016/s0962-8924(24)00125-9","url":null,"abstract":"No Abstract","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":null,"pages":null},"PeriodicalIF":19.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141546835","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}
Pub Date : 2024-07-05DOI: 10.1016/s0962-8924(24)00129-6
No Abstract
无摘要
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/s0962-8924(24)00129-6","DOIUrl":"https://doi.org/10.1016/s0962-8924(24)00129-6","url":null,"abstract":"No Abstract","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":null,"pages":null},"PeriodicalIF":19.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141546837","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}
Pub Date : 2024-07-04DOI: 10.1016/j.tcb.2024.05.005
Victoria Thusgaard Ruhoff, Natascha Leijnse, Amin Doostmohammadi, Poul Martin Bendix
Filopodia, widely distributed on cell surfaces, are distinguished by their dynamic extensions, playing pivotal roles in a myriad of biological processes. Their functions span from mechanosensing and guidance to cell-cell communication during cellular organization in the early embryo. Filopodia have significant roles in pathogenic processes, such as cancer invasion and viral dissemination. Molecular mapping of the filopodome has revealed generic components essential for filopodia functions. In parallel, recent insights into biophysical mechanisms governing filopodia dynamics have provided the foundation for broader investigations of filopodia's biological functions. We highlight recent discoveries of engagement of filopodia in various stages of development and pathogenesis and present an overview of intricate molecular and physical features of these cellular structures across a spectrum of cellular activities.
{"title":"Filopodia: integrating cellular functions with theoretical models.","authors":"Victoria Thusgaard Ruhoff, Natascha Leijnse, Amin Doostmohammadi, Poul Martin Bendix","doi":"10.1016/j.tcb.2024.05.005","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.05.005","url":null,"abstract":"<p><p>Filopodia, widely distributed on cell surfaces, are distinguished by their dynamic extensions, playing pivotal roles in a myriad of biological processes. Their functions span from mechanosensing and guidance to cell-cell communication during cellular organization in the early embryo. Filopodia have significant roles in pathogenic processes, such as cancer invasion and viral dissemination. Molecular mapping of the filopodome has revealed generic components essential for filopodia functions. In parallel, recent insights into biophysical mechanisms governing filopodia dynamics have provided the foundation for broader investigations of filopodia's biological functions. We highlight recent discoveries of engagement of filopodia in various stages of development and pathogenesis and present an overview of intricate molecular and physical features of these cellular structures across a spectrum of cellular activities.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538994","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}
Pub Date : 2024-07-03DOI: 10.1016/j.tcb.2024.06.005
Da Li, Yingqun Huang
Multiple mechanisms have been reported for how circular RNAs (circRNAs) are exported to the cytoplasm. A recent paper by Cao et al. shows that export of a subset of circRNAs with (A)-rich motifs, including one with a clear function, is regulated during neuronal development via a novel mechanism.
{"title":"Regulated circRNA nuclear export in neuronal differentiation","authors":"Da Li, Yingqun Huang","doi":"10.1016/j.tcb.2024.06.005","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.06.005","url":null,"abstract":"<p>Multiple mechanisms have been reported for how circular RNAs (circRNAs) are exported to the cytoplasm. A recent paper by <span>Cao <em>et al.</em></span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"8px\" viewbox=\"0 0 8 8\" width=\"8px\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg> shows that export of a subset of circRNAs with (A)-rich motifs, including one with a clear function, is regulated during neuronal development via a novel mechanism.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":null,"pages":null},"PeriodicalIF":19.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141517066","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}
Pub Date : 2024-07-02DOI: 10.1016/j.tcb.2024.06.003
Alessio Butera, Ivano Amelio
Mutations in the p53 gene compromise its role as guardian of genomic integrity, yielding predominantly missense p53 mutant proteins. The gain-of-function hypothesis has long suggested that these mutant proteins acquire new oncogenic properties; however, recent studies challenge this notion, indicating that targeting these mutants may not impact the fitness of cancer cells. Mounting evidence indicates that tumorigenesis involves a cooperative interplay between driver mutations and cellular state, influenced by developmental stage, external insults, and tissue damage. Consistently, the behavior and properties of p53 mutants are altered by the context. This article aims to provide a balanced summary of the evolving evidence regarding the contribution of p53 mutants in the biology of cancer while contemplating alternative frameworks to decipher the complexity of p53 mutants within their physiological contexts.
{"title":"Deciphering the significance of p53 mutant proteins.","authors":"Alessio Butera, Ivano Amelio","doi":"10.1016/j.tcb.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.tcb.2024.06.003","url":null,"abstract":"<p><p>Mutations in the p53 gene compromise its role as guardian of genomic integrity, yielding predominantly missense p53 mutant proteins. The gain-of-function hypothesis has long suggested that these mutant proteins acquire new oncogenic properties; however, recent studies challenge this notion, indicating that targeting these mutants may not impact the fitness of cancer cells. Mounting evidence indicates that tumorigenesis involves a cooperative interplay between driver mutations and cellular state, influenced by developmental stage, external insults, and tissue damage. Consistently, the behavior and properties of p53 mutants are altered by the context. This article aims to provide a balanced summary of the evolving evidence regarding the contribution of p53 mutants in the biology of cancer while contemplating alternative frameworks to decipher the complexity of p53 mutants within their physiological contexts.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499653","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}
Pub Date : 2024-07-01Epub Date: 2024-05-16DOI: 10.1016/j.tcb.2024.04.006
Clara Mutschler, Stephanie B Telerman
Glial cells have a remarkable plasticity. Recent studies using zebrafish as a model highlight conserved cellular behavior in health and disease in the central nervous system (CNS) between zebrafish and humans. These findings inform our understanding of their function and how their dysregulation in pathogenesis can be determinant.
{"title":"Glial plasticity in the zebrafish central nervous system.","authors":"Clara Mutschler, Stephanie B Telerman","doi":"10.1016/j.tcb.2024.04.006","DOIUrl":"10.1016/j.tcb.2024.04.006","url":null,"abstract":"<p><p>Glial cells have a remarkable plasticity. Recent studies using zebrafish as a model highlight conserved cellular behavior in health and disease in the central nervous system (CNS) between zebrafish and humans. These findings inform our understanding of their function and how their dysregulation in pathogenesis can be determinant.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961092","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}
Pub Date : 2024-07-01Epub Date: 2024-02-23DOI: 10.1016/j.tcb.2024.01.010
Julie Jacquemyn, Isha Ralhan, Maria S Ioannou
Ferroptosis is an oxidative form of iron-dependent cell death characterized by the accumulation of lipid peroxides on membranes. Iron and lipids containing polyunsaturated fatty acids are essential for this process. Ferroptosis is central to several neurological diseases and underlies the importance of balanced iron and polyunsaturated fatty acid metabolism in the brain, particularly in neurons. Here, we reflect on the potential links between neuronal physiology and the accumulation of iron and peroxidated lipids, the mechanisms neurons use to protect themselves from ferroptosis, and the relationship between pathogenic protein deposition and ferroptosis in neurodegenerative disease. We propose that the unique physiology of neurons makes them especially vulnerable to ferroptosis.
{"title":"Driving factors of neuronal ferroptosis.","authors":"Julie Jacquemyn, Isha Ralhan, Maria S Ioannou","doi":"10.1016/j.tcb.2024.01.010","DOIUrl":"10.1016/j.tcb.2024.01.010","url":null,"abstract":"<p><p>Ferroptosis is an oxidative form of iron-dependent cell death characterized by the accumulation of lipid peroxides on membranes. Iron and lipids containing polyunsaturated fatty acids are essential for this process. Ferroptosis is central to several neurological diseases and underlies the importance of balanced iron and polyunsaturated fatty acid metabolism in the brain, particularly in neurons. Here, we reflect on the potential links between neuronal physiology and the accumulation of iron and peroxidated lipids, the mechanisms neurons use to protect themselves from ferroptosis, and the relationship between pathogenic protein deposition and ferroptosis in neurodegenerative disease. We propose that the unique physiology of neurons makes them especially vulnerable to ferroptosis.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":null,"pages":null},"PeriodicalIF":13.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139941261","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}