scholarly journals Dissecting the cell to nucleus, perinucleus and cytosol

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Tattym E. Shaiken ◽  
Antone R. Opekun
Keyword(s):  
Regulation Of Gene Expression ◽  
Genome Integrity ◽  
Perinuclear Region ◽  
Isolation Method ◽  
Total Proteins ◽  
Isolation Technique ◽  
Unknown Composition ◽  
And Function ◽  
P53 Tumor Suppressor Protein

Abstract Cells have been described under the microscope as organelles containing cytoplasm and the nucleus. However, an unnoted structure exists between the cytoplasm and the nucleoplasm of eukaryotic cells. In addition to the nuclear envelope, there exists a perinuclear region (PNR or perinucleus) with unknown composition and function. Until now, an investigation of the role of the perinucleus has been restricted by the absence of a PNR isolation method. This manuscript describes a perinucleus isolation technique on the basis of its unique compact organization. The perinucleus was found to contain approximately 15 to 18% of the total proteins of the mammalian cell, almost half of the proteins of nuclei. Using four different normal and cancer cell lines, it was shown that the composition of PNR is highly dynamic. Application of the method showed that translocation of the p53 tumor-suppressor protein to the perinucleus in immortalized MEF cells is correlated with the translocation of p53-stabilizing protein, nucleophosmin (B23), to the PNR. Herein, the concept of the perinuclear region is advanced as a formal, identifiable structure. The roles of the perinucleus in maintaining genome integrity, regulation of gene expression and understanding of malignant transformation are discussed.

scholarly journals SFPQ Rescues F508del-CFTR Expression and Function in Cystic Fibrosis Bronchial Epithelial Cells

2021 ◽  
Author(s):  
Parameet Kumar ◽  
Dharmendra Kumar Soni ◽  
Chaitali Sen ◽  
Mads B Larsen ◽  
Krystyna Mazan-Mamczarz ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Lung Epithelial Cells ◽  
Regulation Of Expression ◽  
Trafficking Defects ◽  
And Function

Abstract Cystic Fibrosis (CF) occurs as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to misfolding, trafficking defects, and impaired function of the CFTR protein. Splicing factor proline/glutamine-rich (SFPQ) is a multifunctional nuclear RNA-binding protein (RBP) implicated in the regulation of gene expression pathways and intracellular trafficking. Here, we investigated the role of SFPQ in the regulation of the expression and function of F508del-CFTR in CF lung epithelial cells. We find that the expression of SFPQ is reduced in F508del-CFTR CF epithelial cells compared to WT-CFTR control cells. Interestingly, the overexpression of SFPQ in CF cells increases the expression as well as rescues the function of F508del-CFTR. Further, comprehensive transcriptome analyses indicate that SFPQ plays a key role in activating the mutant F508del-CFTR by modulating several cellular signaling pathways. This is the first report on the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung disease. Our findings provide new insights into SFPQ-mediated molecular mechanisms and point to possible novel epigenetic therapeutic targets for CF and related pulmonary diseases.

scholarly journals Critical Role of Types 2 and 3 Deiodinases in the Negative Regulation of Gene Expression by T3 in the Mouse Cerebral Cortex

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2919-2928 ◽  
Author(s):  
Arturo Hernandez ◽  
Beatriz Morte ◽  
Mónica M. Belinchón ◽  
Ainhoa Ceballos ◽  
Juan Bernal
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Thyroid Hormone ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Control Of Gene Expression ◽  
High Doses ◽  
And Function ◽  
Type 3

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T3 to nuclear receptors. Brain T3 concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T4 and T3. We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T3 led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T3 treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T3 action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T3 concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

scholarly journals The role of microRNAs in the legume–Rhizobium nitrogen-fixing symbiosis

2020 ◽  
Vol 71 (5) ◽  
pp. 1668-1680 ◽  
Author(s):  
Nhung T Hoang ◽  
Katalin Tóth ◽  
Gary Stacey
Keyword(s):  
Vascular System ◽  
Regulation Of Gene Expression ◽  
Lotus Japonicus ◽  
Nodule Formation ◽  
Nitrogen Fixing ◽  
Rna Molecules ◽  
Physiological Processes ◽  
Leaf Tissues ◽  
And Function

Abstract Under nitrogen starvation, most legume plants form a nitrogen-fixing symbiosis with Rhizobium bacteria. The bacteria induce the formation of a novel organ called the nodule in which rhizobia reside as intracellular symbionts and convert atmospheric nitrogen into ammonia. During this symbiosis, miRNAs are essential for coordinating the various plant processes required for nodule formation and function. miRNAs are non-coding, endogenous RNA molecules, typically 20–24 nucleotides long, that negatively regulate the expression of their target mRNAs. Some miRNAs can move systemically within plant tissues through the vascular system, which mediates, for example, communication between the stem/leaf tissues and the roots. In this review, we summarize the growing number of miRNAs that function during legume nodulation focusing on two model legumes, Lotus japonicus and Medicago truncatula, and two important legume crops, soybean (Glycine max) and common bean (Phaseolus vulgaris). This regulation impacts a variety of physiological processes including hormone signaling and spatial regulation of gene expression. The role of mobile miRNAs in regulating legume nodule number is also highlighted.

scholarly journals Micro RNAS as New Players in Control of Hypothalamic Functions

2019 ◽  
Vol 9 (2) ◽  
pp. 138-143
Author(s):  
O. A. Beylerli ◽  
I. F. Gareev ◽  
A. T. Beylerli
Keyword(s):  
Regulation Of Gene Expression ◽  
Vital Role ◽  
Key Factors ◽  
Eukaryotic Genes ◽  
Micro Rnas ◽  
A Cell ◽  
The Central Nervous System ◽  
And Function ◽  
Post Transcriptional Regulation

Micro RNAs (miRNAs) are short non-coding RNAs (ncRNAs) of ~22 nucleotides in length involved in the post-transcriptional regulation of gene expression. They were discovered over 15 years ago and their functions are becoming clearer. They play an important role in all biological processes. MiRNAs are important modulators of the expression of eukaryotic genes. Focusing on transcripts encoding proteins they impact on the cellular transcriptome thus helping to determine the destiny of a cell. More and more data emerge to indicate an important functional role of miRNAs in the brain development. Since their discovery many miRNAs have been described as key factors in the development and function of the central nervous system. Some play a significant role in the genesis and differentiation of nerve cells (neurons and glial cells). Notably, it has recently been established that miRNAs play a vital role in the mechanisms underpinning the infantile increase of the gonadotropin-releasing hormone (GnRH) production by neurons in the hypothalamus. This phenomenon is necessary for the onset of puberty in mammals. In this review offers our attempt to describe miRNAs as new players in the control of hypothalamic functions, namely the onset of puberty.

scholarly journals LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during cytokinesis

2017 ◽  
Author(s):  
Ye Hong ◽  
Remi Sonneville ◽  
Bin Wang ◽  
Viktor Scheidt ◽  
Bettina Meier ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Chromosome Structure ◽  
Cleavage Plane ◽  
Genome Integrity ◽  
Human Breast ◽  
Genome Maintenance ◽  
C Elegans ◽  
And Function ◽  
Chromatin Bridges

AbstractFaithful chromosome segregation and genome maintenance requires the removal of all DNA bridges that physically link chromosomes before cells divide. Using C. elegans embryos we show that the LEM-3/Ankle1 nuclease defines a new genome integrity mechanism by processing DNA bridges right before cells divide. LEM-3 acts at the midbody, the structure where abscission occurs at the end of cytokinesis. LEM-3 localization depends on factors needed for midbody assembly, and LEM-3 accumulation is increased and prolonged when chromatin bridges are trapped at the cleavage plane. LEM-3 locally processes chromatin bridges that arise from incomplete DNA replication, unresolved recombination intermediates or the perturbance of chromosome structure. Proper LEM-3 midbody localization and function is regulated by AIR-2/Aurora B kinase. Strikingly, LEM-3 act cooperatively with the BRC-1/BRCA1 homologous recombination factor to promote genome integrity. These findings provide a molecular basis for the suspected role of the LEM-3 orthologue Ankle1 in human breast cancer.

scholarly journals SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Parameet Kumar ◽  
Dharmendra Kumar Soni ◽  
Chaitali Sen ◽  
Mads B. Larsen ◽  
Krystyna Mazan-Mamczarz ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Lung Epithelial Cells ◽  
Regulation Of Expression ◽  
Trafficking Defects ◽  
And Function

AbstractCystic fibrosis (CF) occurs as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to misfolding, trafficking defects, and impaired function of the CFTR protein. Splicing factor proline/glutamine-rich (SFPQ) is a multifunctional nuclear RNA-binding protein (RBP) implicated in the regulation of gene expression pathways and intracellular trafficking. Here, we investigated the role of SFPQ in the regulation of the expression and function of F508del-CFTR in CF lung epithelial cells. We find that the expression of SFPQ is reduced in F508del-CFTR CF epithelial cells compared to WT-CFTR control cells. Interestingly, the overexpression of SFPQ in CF cells increases the expression as well as rescues the function of F508del-CFTR. Further, comprehensive transcriptome analyses indicate that SFPQ plays a key role in activating the mutant F508del-CFTR by modulating several cellular signaling pathways. This is the first report on the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung disease. Our findings provide new insights into SFPQ-mediated molecular mechanisms and point to possible novel epigenetic therapeutic targets for CF and related pulmonary diseases.

scholarly journals Sperm acrosome overgrowth and infertility in mice lacking chromosome 18 pachytene piRNA

2020 ◽  
Author(s):  
Heejin Choi ◽  
Zhengpin Wang ◽  
Jurrien Dean
Keyword(s):  
Ubiquitin Proteasome System ◽  
Genome Integrity ◽  
Male Gametogenesis ◽  
Pirna Cluster ◽  
Ubiquitin Proteasome ◽  
Non Coding Rnas ◽  
Shock Proteins ◽  
And Function ◽  
Golgi Network

AbstractpiRNAs are germline-specific, small non-coding RNAs required to maintain genome integrity and preserve RNA homeostasis during male gametogenesis. In murine adult testes, the highest levels of piRNAs are present in the pachytene stage of meiosis, but their mode of action and function remains incompletely understood. We previously reported that BTBD18 binds to 50 pachytene piRNA-producing loci. Here we show that spermatozoa in gene-edited mice lacking a BTBD18 targeted pachytene piRNA cluster on Chr18 have severe sperm head dysmorphology, poor motility, impaired acrosome exocytosis and are sterile. The absence of Chr18 piRNA results in an imbalance of heat shock proteins associated with renaturing proteins and the ubiquitin-proteasome system involved with protein degradation. The mutant phenotype arises from aberrant formation of proacrosomal vesicles, distortion of the trans-Golgi network, and up-regulation of GOLGA2 associated with acrosome dysgenesis. Collectively, our findings reveal central role of pachytene piRNAs in controlling spermiogenesis and male fertility.

scholarly journals Chromatin Organization and Function in Drosophila

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2362
Author(s):  
Palmira Llorens-Giralt ◽  
Carlos Camilleri-Robles ◽  
Montserrat Corominas ◽  
Paula Climent-Cantó
Keyword(s):  
Cell Nucleus ◽  
Regulation Of Gene Expression ◽  
Temporal Distribution ◽  
Chromatin Organization ◽  
Small Scale ◽  
Nuclear Space ◽  
And Function ◽  
High Order Chromatin ◽  
Eukaryotic Genomes

Eukaryotic genomes are packaged into high-order chromatin structures organized in discrete territories inside the cell nucleus, which is surrounded by the nuclear envelope acting as a barrier. This chromatin organization is complex and dynamic and, thus, determining the spatial and temporal distribution and folding of chromosomes within the nucleus is critical for understanding the role of chromatin topology in genome function. Primarily focusing on the regulation of gene expression, we review here how the genome of Drosophila melanogaster is organized into the cell nucleus, from small scale histone–DNA interactions to chromosome and lamina interactions in the nuclear space.

scholarly journals Sperm acrosome overgrowth and infertility in mice lacking chromosome 18 pachytene piRNA

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009485
Author(s):  
Heejin Choi ◽  
Zhengpin Wang ◽  
Jurrien Dean
Keyword(s):  
Zona Pellucida ◽  
Male Fertility ◽  
Sperm Head ◽  
Genome Integrity ◽  
Male Gametogenesis ◽  
Pirna Cluster ◽  
Non Coding Rnas ◽  
And Function ◽  
Golgi Network

piRNAs are small non-coding RNAs required to maintain genome integrity and preserve RNA homeostasis during male gametogenesis. In murine adult testes, the highest levels of piRNAs are present in the pachytene stage of meiosis, but their mode of action and function remain incompletely understood. We previously reported that BTBD18 binds to 50 pachytene piRNA-producing loci. Here we show that spermatozoa in gene-edited mice lacking a BTBD18 targeted pachytene piRNA cluster on Chr18 have severe sperm head dysmorphology, poor motility, impaired acrosome exocytosis, zona pellucida penetration and are sterile. The mutant phenotype arises from aberrant formation of proacrosomal vesicles, distortion of the trans-Golgi network, and up-regulation of GOLGA2 transcripts and protein associated with acrosome dysgenesis. Collectively, our findings reveal central role of pachytene piRNAs in controlling spermiogenesis and male fertility.

Scanning electron microscopic study of collagen fibrillogenesis and extracellular compartmentalization in the chick embryo tendon

1986 ◽  
Vol 44 ◽  
pp. 208-209
Author(s):  
Grace C.H. Yang
Keyword(s):  
Chick Embryo ◽  
Extracellular Space ◽  
Fibroblast Cell ◽  
Collagen Fibrils ◽  
Electron Microscopic ◽  
Voltage Electron ◽  
Scanning Electron Microscopic Study ◽  
Microscopic Studies ◽  
And Function

The size and organization of collagen fibrils in the extracellular matrix is an important determinant of tissue structure and function. The synthesis and deposition of collagen involves multiple steps which begin within the cell and continue in the extracellular space. High-voltage electron microscopic studies of the chick embryo cornea and tendon suggested that the extracellular space is compartmentalized by the fibroblasts for the regulation of collagen fibril, bundle, and tissue specific macroaggregate formation. The purpose of this study is to gather direct evidence regarding the association of the fibroblast cell surface with newly formed collagen fibrils, and to define the role of the fibroblast in the control and the precise positioning of collagen fibrils, bundles, and macroaggregates during chick tendon development.

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