Nucleus (Austin, Tex.)最新文献_第6页

Lamin B1 overexpression alters chromatin organization and gene expression. 层粘连蛋白B1过表达改变染色质组织和基因表达。

Nucleus (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19491034.2023.2202548

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":"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.","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}

引用次数: 2

Transcriptional condensates and phase separation: condensing information across scales and mechanisms. 转录缩合物和相分离：跨尺度和机制的信息浓缩。

Nucleus (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19491034.2023.2213551

Justin Demmerle, Siyuan Hao, Danfeng Cai

{"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":"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.","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}

引用次数: 0

Plant nuclear envelope as a hub connecting genome organization with regulation of gene expression. 植物核膜是连接基因组组织与基因表达调控的枢纽。

Nucleus (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19491034.2023.2178201

Yu Tang

引用次数: 0

Prelamin A and ZMPSTE24 in premature and physiological aging. Prelamin A和ZMPSTE24在早衰和生理衰老中的作用。

Nucleus (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-10-26 DOI: 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":"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 LMNA and ZMPSTE24 is disruption of the final posttranslational processing step in the production of the nuclear scaffold protein lamin A. LMNA encodes the lamin A precursor, prelamin A and ZMPSTE24 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 (LmnaL648R/L648R) 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.","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}

引用次数: 0

Revisiting the truncated lamin A produced by a commonly used strain of Lmna knockout mice. 对一种常用的Lmna基因敲除小鼠产生的截短的层粘连蛋白A进行重新研究。

Nucleus (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-09-27 DOI: 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 Lmna 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":"The Lmna knockout mouse (Lmna-/-) created by Sullivan and coworkers in 1999 has been widely used to examine lamin A/C function. The knockout allele contains a deletion of Lmna 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 Lmna cDNA containing exon 1-7 + exon 12 sequences. Because exon 12 encodes prelamin A's CaaX motif, the mutant lamin A is assumed to be farnesylated. In the current study, we found that the truncated lamin A in Lmna-/- 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 Lmna transcripts in Lmna-/- 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 Lmna-/- 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 Lmna-/- MEFs and adds to our understanding of a commonly used strain of Lmna-/- mice.","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}

引用次数: 0

Beyond ribosome biogenesis: noncoding nucleolar RNAs in physiology and tumor biology. 核糖体生物发生之外：生理学和肿瘤生物学中的非编码核仁RNA。

Nucleus (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-10-31 DOI: 10.1080/19491034.2023.2274655

Nuray Böğürcü-Seidel, Nadja Ritschel, Till Acker, Attila Németh

引用次数: 0

Nuclear envelope budding and its cellular functions. 核膜出芽及其细胞功能。

Nucleus (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19491034.2023.2178184

Katharina S Keuenhof, Verena Kohler, Filomena Broeskamp, Dimitra Panagaki, Sean D Speese, Sabrina Büttner, Johanna L Höög

引用次数: 0

CiRS-7 Enhances the Liquid-liquid Phase Separation of miRISC and Promotes DNA Damage Repair. CiRS-7 可增强 miRISC 的液-液相分离并促进 DNA 损伤修复。

IF 4.5

Nucleus (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-12-17 DOI: 10.1080/19491034.2023.2293599

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

{"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":"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 in vivo and in vitro 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.","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"14 1","pages":"2293599"},"PeriodicalIF":4.5,"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}

引用次数: 0

The farnesyl transferase inhibitor (FTI) lonafarnib improves nuclear morphology in ZMPSTE24-deficient fibroblasts from patients with the progeroid disorder MAD-B. 法尼基转移酶抑制剂（FTI）lonafarnib可改善类早衰症MAD-B患者ZMPSTE24缺陷成纤维细胞的核形态。

IF 4.5

Nucleus (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-12-05 DOI: 10.1080/19491034.2023.2288476

Kamsi O Odinammadu, Khurts Shilagardi, Kelsey Tuminelli, Daniel P Judge, Leslie B Gordon, Susan Michaelis

{"title":"The farnesyl transferase inhibitor (FTI) lonafarnib improves nuclear morphology in ZMPSTE24-deficient fibroblasts from patients with the progeroid disorder MAD-B.","authors":"Kamsi O Odinammadu, Khurts Shilagardi, Kelsey Tuminelli, Daniel P Judge, Leslie B Gordon, Susan Michaelis","doi":"10.1080/19491034.2023.2288476","DOIUrl":"10.1080/19491034.2023.2288476","url":null,"abstract":"Several related progeroid disorders are caused by defective post-translational processing of prelamin A, the precursor of the nuclear scaffold protein lamin A, encoded by LMNA. Prelamin A undergoes farnesylation and additional modifications at its C-terminus. Subsequently, the farnesylated C-terminal segment is cleaved off by the zinc metalloprotease ZMPSTE24. The premature aging disorder Hutchinson Gilford progeria syndrome (HGPS) and a related progeroid disease, mandibuloacral dysplasia (MAD-B), are caused by mutations in LMNA and ZMPSTE24, respectively, that result in failure to process the lamin A precursor and accumulate permanently farnesylated forms of prelamin A. The farnesyl transferase inhibitor (FTI) lonafarnib is known to correct the aberrant nuclear morphology of HGPS patient cells and improves lifespan in children with HGPS. Importantly, and in contrast to a previous report, we show here that FTI treatment also improves the aberrant nuclear phenotypes in MAD-B patient cells with mutations in ZMPSTE24 (P248L or L425P). As expected, lonafarnib does not correct nuclear defects for cells with lamin A processing-proficient mutations. We also examine prelamin A processing in fibroblasts from two individuals with a prevalent laminopathy mutation LMNA-R644C. Despite the proximity of residue R644 to the prelamin A cleavage site, neither R644C patient cell line shows a prelamin A processing defect, and both have normal nuclear morphology. This work clarifies the prelamin A processing status and role of FTIs in a variety of laminopathy patient cells and supports the FDA-approved indication for the FTI Zokinvy for patients with processing-deficient progeroid laminopathies, but not for patients with processing-proficient laminopathies.","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"14 1","pages":"2288476"},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138489229","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}

引用次数: 0

Nucleus-wide analysis of coherent RNA pol II movement in the context of chromatin dynamics in living cancer cells. 活癌细胞染色质动力学背景下相干RNA pol II运动的全核分析。

Nucleus (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19491034.2022.2157133

Haitham A Shaban

引用次数: 0