Nucleus (Austin, Tex.)最新文献_第6页

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。

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":0.0,"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

Architectural control of mesenchymal stem cell phenotype through nuclear actin. 通过核肌动蛋白对间充质干细胞表型进行结构控制。

Nucleus (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19491034.2022.2029297

Janet Rubin, Andre J van Wijnen, Gunes Uzer

引用次数: 0

Aberrant chromatin organization at the nexus of laminopathy disease pathways. 板层病疾病通路的染色质组织异常。

Nucleus (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19491034.2022.2153564

Garrett T Santini, Parisha P Shah, Ashley Karnay, Rajan Jain

引用次数: 0

Cell cycle control of kinetochore assembly. 着丝点组装的细胞周期控制。

Nucleus (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19491034.2022.2115246

Qianhua Dong, Fei Li

引用次数: 1

Chromatin accessibility: methods, mechanisms, and biological insights. 染色质可及性：方法、机制和生物学见解。

Nucleus (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19491034.2022.2143106

Andrés R Mansisidor, Viviana I Risca

引用次数: 0

Spelling out the roles of individual nucleoporins in nuclear export of mRNA. 阐明各个核蛋白在 mRNA 核输出中的作用。

Nucleus (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19491034.2022.2076965

Mark Tingey, Yichen Li, Wenlan Yu, Albert Young, Weidong Yang

引用次数: 0

MeCP2-induced heterochromatin organization is driven by oligomerization-based liquid-liquid phase separation and restricted by DNA methylation. mecp2诱导的异染色质组织由基于寡聚化的液-液相分离驱动，并受到DNA甲基化的限制。

Nucleus (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19491034.2021.2024691

Hui Zhang, Hector Romero, Annika Schmidt, Katalina Gagova, Weihua Qin, Bianca Bertulat, Anne Lehmkuhl, Manuela Milden, Malte Eck, Tobias Meckel, Heinrich Leonhardt, M Cristina Cardoso

{"title":"MeCP2-induced heterochromatin organization is driven by oligomerization-based liquid-liquid phase separation and restricted by DNA methylation.","authors":"Hui Zhang, Hector Romero, Annika Schmidt, Katalina Gagova, Weihua Qin, Bianca Bertulat, Anne Lehmkuhl, Manuela Milden, Malte Eck, Tobias Meckel, Heinrich Leonhardt, M Cristina Cardoso","doi":"10.1080/19491034.2021.2024691","DOIUrl":"https://doi.org/10.1080/19491034.2021.2024691","url":null,"abstract":"Heterochromatin is the highly compacted form of chromatin with various condensation levels hallmarked by high DNA methylation. MeCP2 is mostly known as a DNA methylation reader but has also been reported as a heterochromatin organizer. Here, we combine liquid-liquid phase separation (LLPS) analysis and single-molecule tracking with quantification of local MeCP2 concentrations in vitro and in vivo to explore the mechanism of MeCP2-driven heterochromatin organization and dynamics. We show that MeCP2 alone forms liquid-like spherical droplets via multivalent electrostatic interactions and with isotropic mobility. Crowded environments and DNA promote MeCP2 LLPS and slow down MeCP2 mobility. DNA methylation, however, restricts the growth of heterochromatin compartments correlating with immobilization of MeCP2. Furthermore, MeCP2 self-interaction is required for LLPS and is disrupted by Rett syndrome mutations. In summary, we are able to model the heterochromatin compartmentalization as well as MeCP2 concentration and heterogeneous motion in the minimal in vitro system.","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"1-34"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/0d/KNCL_13_2024691.PMC8855868.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39916427","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: 10

A-type lamins involvement in transport and implications in cancer? a型层粘连蛋白参与运输及其对癌症的影响?

Nucleus (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19491034.2022.2118418

Nicholas R Scott, Sapun H Parekh

引用次数: 0

Autophagy regulates rRNA synthesis. 自噬调节rRNA合成。

Nucleus (Austin, Tex.) Pub Date : 2022-12-01 DOI: 10.1080/19491034.2022.2114661

Yinfeng Xu, Wei Wan

{"title":"Autophagy regulates rRNA synthesis.","authors":"Yinfeng Xu, Wei Wan","doi":"10.1080/19491034.2022.2114661","DOIUrl":"https://doi.org/10.1080/19491034.2022.2114661","url":null,"abstract":"Autophagy has emerged as a key regulator of cell metabolism. Recently, we have demonstrated that autophagy is involved in RNA metabolism by regulating ribosomal RNA (rRNA) synthesis. We found that autophagy-deficient cells display much higher 47S precursor rRNA level, which is caused by the accumulation of SQSTM1/p62 (sequestosome 1) but not other autophagy receptors. Mechanistically, SQSTM1 accumulation potentiates the activation of MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) signaling, which facilitates the assembly of RNA polymerase I pre-initiation complex at ribosomal DNA (rDNA) promoter regions and leads to the activation of rDNA transcription. Finally, we showed that SQSTM1 accumulation is responsible for the increase in protein synthesis, cell growth and cell proliferation in autophagy-deficient cells. Taken together, our findings reveal a regulatory role of autophagy and autophagy receptor SQSTM1 in rRNA synthesis and may provide novel mechanisms for the hyperactivated rDNA transcription in autophagy-related human diseases.Abbreviations: 5-FUrd: 5-fluorouridine; LAP: MAP1LC3/LC3-associated phagocytosis; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PIC: pre-initiation complex; POLR1: RNA polymerase I; POLR1A: RNA polymerase I subunit A; rDNA: ribosomal DNA; RRN3: RRN3 homolog, RNA polymerase I transcription factor; rRNA: ribosomal RNA; SQSTM1/p62: sequestosome 1; TP53INP2: tumor protein p53 inducible nuclear protein 2; UBTF: upstream binding transcription factor.","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"13 1","pages":"203-207"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9415535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9180216","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: 1