Nucleus (Austin, Tex.)Pub Date : 2024-12-01Epub Date: 2024-12-02DOI: 10.1080/19491034.2024.2431239
Christina Rabeler, Nicholas Paterna, Rajiv Potluri, Lia R D'Alessandro, Anusha Bhatia, Shu Yi Chen, Johanna Lee, Bereketab Abeje, Benjamin Lipchin, Benjamin R Carone, Dawn M Carone
{"title":"Locus-specific differential expression of human satellite sequences in the nuclei of cancer cells and heat-shocked cells.","authors":"Christina Rabeler, Nicholas Paterna, Rajiv Potluri, Lia R D'Alessandro, Anusha Bhatia, Shu Yi Chen, Johanna Lee, Bereketab Abeje, Benjamin Lipchin, Benjamin R Carone, Dawn M Carone","doi":"10.1080/19491034.2024.2431239","DOIUrl":"10.1080/19491034.2024.2431239","url":null,"abstract":"<p><p>Human satellitess(HSats) are pericentric, tandemly repeating satellite DNA sequences in the human genome. While silent in normal cells, a subset of HSat2 noncoding RNA is expressed and accumulates in the nucleus of cancer cells. We developed a FISH-based approach for identification of the distribution of three subfamilies of HSat2 (A1, A2, B) sequences on individual human chromosomes. Further, using the HSat subfamily annotations in the T2T completed centromere satellite (CenSat) sequence, we isolated, defined and mapped differentially expressed sequence variants of nuclear-restricted HSat2 and HSat3 RNA from cancer cell lines and heat-shocked cells. We identified chromosome-specific and subfamily-specific expression of HSat2 and HSat3 and established a computational pipeline for differential expression analysis of tandemly repeated satellite sequences. Results suggest the differential expression of chromosome-specific HSat2 arrays in the human genome may underlie their accumulation in cancer cells and that specific HSat3 loci are upregulated upon heat shock.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"15 1","pages":"2431239"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeanae M Kaneshiro, Juliana S Capitanio, Martin W Hetzer
{"title":"Lamin B1 overexpression alters chromatin organization and gene expression.","authors":"Jeanae M Kaneshiro, Juliana S Capitanio, Martin W Hetzer","doi":"10.1080/19491034.2023.2202548","DOIUrl":"10.1080/19491034.2023.2202548","url":null,"abstract":"<p><p>Peripheral heterochromatin positioning depends on nuclear envelope associated proteins and repressive histone modifications. Here we show that overexpression (OE) of Lamin B1 (LmnB1) leads to the redistribution of peripheral heterochromatin into heterochromatic foci within the nucleoplasm. These changes represent a perturbation of heterochromatin binding at the nuclear periphery (NP) through a mechanism independent from altering other heterochromatin anchors or histone post-translational modifications. We further show that LmnB1 OE alters gene expression. These changes do not correlate with different levels of H3K9me3, but a significant number of the misregulated genes were likely mislocalized away from the NP upon LmnB1 OE. We also observed an enrichment of developmental processes amongst the upregulated genes. ~74% of these genes were normally repressed in our cell type, suggesting that LmnB1 OE promotes gene de-repression. This demonstrates a broader consequence of LmnB1 OE on cell fate, and highlights the importance of maintaining proper levels of LmnB1.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"14 1","pages":"2202548"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/66/KNCL_14_2202548.PMC10114975.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9569809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcriptional condensates and phase separation: condensing information across scales and mechanisms.","authors":"Justin Demmerle, Siyuan Hao, Danfeng Cai","doi":"10.1080/19491034.2023.2213551","DOIUrl":"10.1080/19491034.2023.2213551","url":null,"abstract":"<p><p>Transcription is the fundamental process of gene expression, which in eukaryotes occurs within the complex physicochemical environment of the nucleus. Decades of research have provided extreme detail in the molecular and functional mechanisms of transcription, but the spatial and genomic organization of transcription remains mysterious. Recent discoveries show that transcriptional components can undergo phase separation and create distinct compartments inside the nucleus, providing new models through which to view the transcription process in eukaryotes. In this review, we focus on transcriptional condensates and their phase separation-like behaviors. We suggest differentiation between physical descriptions of phase separation and the complex and dynamic biomolecular assemblies required for productive gene expression, and we discuss how transcriptional condensates are central to organizing the three-dimensional genome across spatial and temporal scales. Finally, we map approaches for therapeutic manipulation of transcriptional condensates and ask what technical advances are needed to understand transcriptional condensates more completely.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"14 1","pages":"2213551"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/e3/KNCL_14_2213551.PMC10208215.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9944736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Plant nuclear envelope as a hub connecting genome organization with regulation of gene expression.","authors":"Yu Tang","doi":"10.1080/19491034.2023.2178201","DOIUrl":"10.1080/19491034.2023.2178201","url":null,"abstract":"<p><p>Eukaryotic cells organize their genome within the nucleus with a double-layered membrane structure termed the nuclear envelope (NE) as the physical barrier. The NE not only shields the nuclear genome but also spatially separates transcription from translation. Proteins of the NE including nucleoskeleton proteins, inner nuclear membrane proteins, and nuclear pore complexes have been implicated in interacting with underlying genome and chromatin regulators to establish a higher-order chromatin architecture. Here, I summarize recent advances in the knowledge of NE proteins that are involved in chromatin organization, gene regulation, and coordination of transcription and mRNA export. These studies support an emerging view of plant NE as a central hub that contributes to chromatin organization and gene expression in response to various cellular and environmental cues.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"14 1","pages":"2178201"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9387547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2023-12-01Epub Date: 2023-10-26DOI: 10.1080/19491034.2023.2270345
Howard J Worman, Susan Michaelis
{"title":"Prelamin A and ZMPSTE24 in premature and physiological aging.","authors":"Howard J Worman, Susan Michaelis","doi":"10.1080/19491034.2023.2270345","DOIUrl":"10.1080/19491034.2023.2270345","url":null,"abstract":"<p><p>As human longevity increases, understanding the molecular mechanisms that drive aging becomes ever more critical to promote health and prevent age-related disorders. Premature aging disorders or progeroid syndromes can provide critical insights into aspects of physiological aging. A major cause of progeroid syndromes which result from mutations in the genes <i>LMNA</i> and <i>ZMPSTE24</i> is disruption of the final posttranslational processing step in the production of the nuclear scaffold protein lamin A. <i>LMNA</i> encodes the lamin A precursor, prelamin A and <i>ZMPSTE24</i> encodes the prelamin A processing enzyme, the zinc metalloprotease ZMPSTE24. Progeroid syndromes resulting from mutations in these genes include the clinically related disorders Hutchinson-Gilford progeria syndrome (HGPS), mandibuloacral dysplasia-type B, and restrictive dermopathy. These diseases have features that overlap with one another and with some aspects of physiological aging, including bone defects resembling osteoporosis and atherosclerosis (the latter primarily in HGPS). The progeroid syndromes have ignited keen interest in the relationship between defective prelamin A processing and its accumulation in normal physiological aging. In this review, we examine the hypothesis that diminished processing of prelamin A by ZMPSTE24 is a driver of physiological aging. We review features a new mouse (<i>Lmna</i><sup>L648R/L648R</sup>) that produces solely unprocessed prelamin A and provides an ideal model for examining the effects of its accumulation during aging. We also discuss existing data on the accumulation of prelamin A or its variants in human physiological aging, which call out for further validation and more rigorous experimental approaches to determine if prelamin A contributes to normal aging.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"14 1","pages":"2270345"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2023-12-01Epub Date: 2023-09-27DOI: 10.1080/19491034.2023.2262308
Joonyoung R Kim, Paul H Kim, Ashley Presnell, Yiping Tu, Stephen G Young
{"title":"Revisiting the truncated lamin A produced by a commonly used strain of <i>Lmna</i> knockout mice.","authors":"Joonyoung R Kim, Paul H Kim, Ashley Presnell, Yiping Tu, Stephen G Young","doi":"10.1080/19491034.2023.2262308","DOIUrl":"10.1080/19491034.2023.2262308","url":null,"abstract":"<p><p>The <i>Lmna</i> knockout mouse (<i>Lmna</i><sup>-/-</sup>) created by Sullivan and coworkers in 1999 has been widely used to examine lamin A/C function. The knockout allele contains a deletion of <i>Lmna</i> intron 7-exon 11 sequences and was reported to be a null allele. Later, Jahn and coworkers discovered that the mutant allele produces a 54-kDa truncated lamin A and identified, by RT-PCR, a <i>Lmna</i> cDNA containing exon 1-7 + exon 12 sequences. Because exon 12 encodes prelamin A's <i>CaaX</i> motif, the mutant lamin A is assumed to be farnesylated. In the current study, we found that the truncated lamin A in <i>Lmna</i><sup>-/-</sup> mouse embryonic fibroblasts (MEFs) was predominantly nucleoplasmic rather than at the nuclear rim, leading us to hypothesize that it was not farnesylated. Our study revealed that the most abundant <i>Lmna</i> transcripts in <i>Lmna</i><sup>-/-</sup> MEFs contain exon 1-7 but not exon 12 sequences. Exon 1-7 + exon 12 transcripts were detectable by PCR but in trace amounts. We suspect that these findings explain the nucleoplasmic distribution of the truncated lamin A in <i>Lmna</i><sup>-/-</sup> MEFs, and subsequent cell transduction experiments support this suspicion. A truncated lamin A containing exon 1-7 sequence was nucleoplasmic, whereas a lamin A containing exon 1-7 + exon 12 sequences was located along the nuclear rim. Our study explains the nucleoplasmic targeting of truncated lamin A in <i>Lmna</i><sup>-/-</sup> MEFs and adds to our understanding of a commonly used strain of <i>Lmna</i><sup>-/-</sup> mice.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"14 1","pages":"2262308"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bc/ad/KNCL_14_2262308.PMC10538457.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41159426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2023-12-01Epub Date: 2023-10-31DOI: 10.1080/19491034.2023.2274655
Nuray Böğürcü-Seidel, Nadja Ritschel, Till Acker, Attila Németh
{"title":"Beyond ribosome biogenesis: noncoding nucleolar RNAs in physiology and tumor biology.","authors":"Nuray Böğürcü-Seidel, Nadja Ritschel, Till Acker, Attila Németh","doi":"10.1080/19491034.2023.2274655","DOIUrl":"10.1080/19491034.2023.2274655","url":null,"abstract":"<p><p>The nucleolus, the largest subcompartment of the nucleus, stands out from the nucleoplasm due to its exceptionally high local RNA and low DNA concentrations. Within this central hub of nuclear RNA metabolism, ribosome biogenesis is the most prominent ribonucleoprotein (RNP) biogenesis process, critically determining the structure and function of the nucleolus. However, recent studies have shed light on other roles of the nucleolus, exploring the interplay with various noncoding RNAs that are not directly involved in ribosome synthesis. This review focuses on this intriguing topic and summarizes the techniques to study and the latest findings on nucleolar long noncoding RNAs (lncRNAs) as well as microRNAs (miRNAs) in the context of nucleolus biology beyond ribosome biogenesis. We particularly focus on the multifaceted roles of the nucleolus and noncoding RNAs in physiology and tumor biology.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"14 1","pages":"2274655"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katharina S Keuenhof, Verena Kohler, Filomena Broeskamp, Dimitra Panagaki, Sean D Speese, Sabrina Büttner, Johanna L Höög
{"title":"Nuclear envelope budding and its cellular functions.","authors":"Katharina S Keuenhof, Verena Kohler, Filomena Broeskamp, Dimitra Panagaki, Sean D Speese, Sabrina Büttner, Johanna L Höög","doi":"10.1080/19491034.2023.2178184","DOIUrl":"10.1080/19491034.2023.2178184","url":null,"abstract":"<p><p>The nuclear pore complex (NPC) has long been assumed to be the sole route across the nuclear envelope, and under normal homeostatic conditions it is indeed the main mechanism of nucleo-cytoplasmic transport. However, it has also been known that e.g. herpesviruses cross the nuclear envelope utilizing a pathway entitled nuclear egress or envelopment/de-envelopment. Despite this, a thread of observations suggests that mechanisms similar to viral egress may be transiently used also in healthy cells. It has since been proposed that mechanisms like nuclear envelope budding (NEB) can facilitate the transport of RNA granules, aggregated proteins, inner nuclear membrane proteins, and mis-assembled NPCs. Herein, we will summarize the known roles of NEB as a physiological and intrinsic cellular feature and highlight the many unanswered questions surrounding these intriguing nuclear events.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"14 1","pages":"2178184"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9371338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CiRS-7 Enhances the Liquid-liquid Phase Separation of miRISC and Promotes DNA Damage Repair.","authors":"Yun-Long Wang, Li-Li Feng, Jie Shi, Wan-Ying Chen, Shu-Ying Bie, Shao-Mei Bai, Guang-Dong Zeng, Rui-Zhi Wang, Jian Zheng, Xiang-Bo Wan, Xin-Juan Fan","doi":"10.1080/19491034.2023.2293599","DOIUrl":"10.1080/19491034.2023.2293599","url":null,"abstract":"<p><p>Noncoding RNAs have been found to play important roles in DNA damage repair, whereas the participation of circRNA remains undisclosed. Here, we characterized ciRS-7, a circRNA containing over 70 putative miR-7-binding sites, as an enhancer of miRISC condensation and DNA repair. Both <i>in vivo</i> and <i>in vitro</i> experiments confirmed the condensation of TNRC6B and AGO2, two core protein components of human miRISC. Moreover, overexpressing ciRS-7 largely increased the condensate number of TNRC6B and AGO2 in cells, while silencing ciRS-7 reduced it. Additionally, miR-7 overexpression also promoted miRISC condensation. Consistent with the previous report that AGO2 participated in RAD51-mediated DNA damage repair, the overexpression of ciRS-7 significantly promoted irradiation-induced DNA damage repair by enhancing RAD51 recruitment. Our results uncover a new role of circRNA in liquid-liquid phase separation and provide new insight into the regulatory mechanism of ciRS-7 on miRISC function and DNA repair.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"14 1","pages":"2293599"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}