scholarly journals Divide and Rule: Phase Separation in Eukaryotic Genome Functioning

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2480
Author(s):  
Sergey V. Razin ◽  
Sergey V. Ulianov
Keyword(s):  
Phase Separation ◽  
Cellular Localization ◽  
Spatial Organization ◽  
Regulation Of Gene Expression ◽  
Size Composition ◽  
Nuclear Bodies ◽  
Eukaryotic Chromatin ◽  
A Cell ◽  
Divide And Rule

The functioning of a cell at various organizational levels is determined by the interactions between macromolecules that promote cellular organelle formation and orchestrate metabolic pathways via the control of enzymatic activities. Although highly specific and relatively stable protein-protein, protein-DNA, and protein-RNA interactions are traditionally suggested as the drivers for cellular function realization, recent advances in the discovery of weak multivalent interactions have uncovered the role of so-called macromolecule condensates. These structures, which are highly divergent in size, composition, function, and cellular localization are predominantly formed by liquid-liquid phase separation (LLPS): a physical-chemical process where an initially homogenous solution turns into two distinct phases, one of which contains the major portion of the dissolved macromolecules and the other one containing the solvent. In a living cell, LLPS drives the formation of membrane-less organelles such as the nucleolus, nuclear bodies, and viral replication factories and facilitates the assembly of complex macromolecule aggregates possessing regulatory, structural, and enzymatic functions. Here, we discuss the role of LLPS in the spatial organization of eukaryotic chromatin and regulation of gene expression in normal and pathological conditions.

scholarly journals Chromatin is an ancient innovation conserved between Archaea and Eukarya

eLife ◽  
2012 ◽  
Vol 1 ◽  
Author(s):  
Ron Ammar ◽  
Dax Torti ◽  
Kyle Tsui ◽  
Marinella Gebbia ◽  
Tanja Durbic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Nucleosome Occupancy ◽  
Regulation Of Gene Expression ◽  
Haloferax Volcanii ◽  
Dna Compaction ◽  
Genome Wide ◽  
Eukaryotic Chromatin ◽  
Transcriptional Start Sites

The eukaryotic nucleosome is the fundamental unit of chromatin, comprising a protein octamer that wraps ∼147 bp of DNA and has essential roles in DNA compaction, replication and gene expression. Nucleosomes and chromatin have historically been considered to be unique to eukaryotes, yet studies of select archaea have identified homologs of histone proteins that assemble into tetrameric nucleosomes. Here we report the first archaeal genome-wide nucleosome occupancy map, as observed in the halophile Haloferax volcanii. Nucleosome occupancy was compared with gene expression by compiling a comprehensive transcriptome of Hfx. volcanii. We found that archaeal transcripts possess hallmarks of eukaryotic chromatin structure: nucleosome-depleted regions at transcriptional start sites and conserved −1 and +1 promoter nucleosomes. Our observations demonstrate that histones and chromatin architecture evolved before the divergence of Archaea and Eukarya, suggesting that the fundamental role of chromatin in the regulation of gene expression is ancient.

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 SPATIAL ORGANIZATION OF TRANSCRIBED EUKARYOTIC GENES

2020 ◽  
Author(s):  
Susanne Leidescher ◽  
Johannes Nübler ◽  
Yana Feodorova ◽  
Erica Hildebrand ◽  
Simon Ullrich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spatial Organization ◽  
Regulation Of Gene Expression ◽  
Spatial Arrangement ◽  
Eukaryotic Genes ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Intrinsic Stiffness ◽  
Established Role

SUMMARYDespite the well established role of nuclear organization in the regulation of gene expression, little is known about the reverse: how transcription shapes the spatial organization of the genome. In particular, given the relatively small sizes of genes and the limited resolution of light microscopy, the structure and spatial arrangement of a single transcribed gene are still poorly understood. Here, we make use of several long highly expressed mammalian genes and demonstrate that they form Transcription Loops (TLs) with polymerases moving along the loops and carrying nascent RNAs that undergo co-transcriptional splicing. TLs dynamically modify their harboring loci and extend into the nuclear interior suggesting an intrinsic stiffness. Both experimental evidence and polymer modeling support the hypothesis that TL stiffness is caused by the dense decoration of transcribed genes with multiple voluminous nascent RNPs. We propose that TL formation is a universal principle of eukaryotic gene expression.

scholarly journals Nuclear myosin VI regulates the spatial organization of mammalian transcription initiation

2020 ◽  
Author(s):  
Yukti Hari-Gupta ◽  
Natalia Fili ◽  
Ália dos Santos ◽  
Alexander W. Cook ◽  
Rosemarie E. Gough ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Mammalian Cells ◽  
Spatial Organization ◽  
Regulation Of Gene Expression ◽  
Myosin Vi ◽  
Transcription Factories ◽  
Cellular Environment

SUMMARYDuring transcription, RNA Polymerase II (RNAPII) is spatially organised within the nucleus into clusters that correlate with transcription activity. While this is a hallmark of genome regulation in mammalian cells, the mechanisms concerning the assembly, organisation and stability which underpin the function these transcription factories remain unknown. Here, we have used combination of single molecule imaging and genomic approaches to explore the role of nuclear myosin VI in the nanoscale organisation of RNAPII. We reveal that myosin VI acts as the molecular anchor that holds RNAPII into transcription factories. Perturbation of myosin VI leads to the disruption of RNAPII localisation, changes in chromatin organisation and subsequently a decrease in gene expression. Overall, we uncover the fundamental role of myosin VI in the spatial regulation of gene expression during the rapid response to changes in the cellular environment.

scholarly journals Confinement size determines the architecture of Ran-induced microtubule networks

2020 ◽  
Author(s):  
Ya Gai ◽  
Sagar Setru ◽  
Brian Cook ◽  
Howard A. Stone ◽  
Sabine Petry
Keyword(s):  
Mitotic Spindle ◽  
Spatial Organization ◽  
Droplet Diameter ◽  
Network Architectures ◽  
Simple Strategy ◽  
Egg Extracts ◽  
A Cell ◽  
Mitotic Spindle Assembly ◽  
Microtubule Networks

ABSTRACTThe organization of microtubules (MTs) within cells is critical for its internal organization during interphase and mitosis. During mitotic spindle assembly, MTs are made and organized around chromosomes in a process regulated by RanGTP. The role of RanGTP has been explored in Xenopus egg extracts, which are not limited by a cell membrane. Here, we investigated whether cell-sized confinements affect the assembly of RanGTP-induced MT networks in Xenopus egg extracts. We used microfluidics to encapsulate extract within monodisperse extract-in-oil droplets. Importantly, we find that the architecture of Ran-induced MT networks depends on the droplet diameter and the Ran concentration, and differs from structures formed in bulk extract. Our results highlight that both MT nucleation and physical confinement play critical roles in determining the spatial organization of the MT cytoskeleton.STATEMENT OF SIGNIFICANCEDuring cell division, chromosomes are segregated by the mitotic spindle, whose framework consists of up to hundreds of thousands of microtubules (MTs). Spindle MTs are generated via several pathways, one of which is regulated by RanGTP. Yet, how Ran-induced MTs self-organize within cell-sized confinement remains unclear. This work reports unexpected architectures of Ran-induced MT networks confined in cell-sized droplets, which depend on the droplet diameter and the RanGTP concentration. Thus, MT nucleation and confinement together give rise to specific MT network architectures, which are otherwise not observed in unconfined assays. The findings provide a simple strategy to engineer the architectures of MT networks and could have direct implications in nucleation-controlled soft material processing.

scholarly journals Role of ACE2/TMPRSS2 genes regulation by intestinal microRNA isoforms in the COVID-19 pathogenesis

2020 ◽  
Author(s):  
SA Nersisyan ◽  
MYu Shkurnikov ◽  
AI Osipyants ◽  
VI Vechorko
Keyword(s):  
Regulation Of Gene Expression ◽  
Surface Proteins ◽  
Sequencing Data ◽  
Angiotensin Converting Enzyme 2 ◽  
Mirna Sequencing ◽  
A Cell ◽  
Regulation Mechanisms ◽  
Transmembrane Serine Protease ◽  
High Level

Coronavirus SARS-CoV-2, the cause of the COVID-19 pandemic, enters the cell by binding the cell surface proteins: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The expression of these proteins varies significantly in individual organs and tissues of the human body. One of the proteins’ expression regulation mechanisms is based on the activity of the microRNA (miRNA) molecules, small non-coding RNAs, the most important function of which is the post-transcriptional negative regulation of gene expression. The study was aimed to investigate the mechanisms of the interactions between miRNA isoforms and ACE2/TMPRSS2 genes in the colon tissues known for the high level of expression of the described enzymes. The search for interactions was performed using the correlation analysis applied to the publicly available paired mRNA/miRNA sequencing data of colon tissues. Among the others, such miRNAs as miR-30c and miR-200c were identified known for their involvement in the coronavirus infection and acute respiratory distress syndrome pathogenesis. Thus, new potential mechanisms for the ACE2 and TMPRSS2 enzymes regulation were ascertained, as well as their possible functional activity in a cell infected with coronavirus.

The Role of microRNAs in the Viral Infections

2019 ◽  
Vol 24 (39) ◽  
pp. 4659-4667 ◽  
Author(s):  
Mona Fani ◽  
Milad Zandi ◽  
Majid Rezayi ◽  
Nastaran Khodadad ◽  
Hadis Langari ◽  
...  
Keyword(s):  
Viral Infections ◽  
Rna Viruses ◽  
Regulation Of Gene Expression ◽  
Molecular Structures ◽  
Main Function ◽  
Cellular Functions ◽  
Viral Genes ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.

CD38 as an immunomodulator in cancer

2020 ◽  
Vol 16 (34) ◽  
pp. 2853-2861
Author(s):  
Yanli Li ◽  
Rui Yang ◽  
Limo Chen ◽  
Sufang Wu
Keyword(s):  
Multiple Myeloma ◽  
Cell Activation ◽  
Human Tissues ◽  
Transmembrane Glycoprotein ◽  
Cell Activation Marker ◽  
Research Findings ◽  
A Cell ◽  
And Function ◽  
Human Molecule

CD38 is a transmembrane glycoprotein that is widely expressed in a variety of human tissues and cells, especially those in the immune system. CD38 protein was previously considered as a cell activation marker, and today monoclonal antibodies targeting CD38 have witnessed great achievements in multiple myeloma and promoted researchers to conduct research on other tumors. In this review, we provide a wide-ranging review of the biology and function of the human molecule outside the field of myeloma. We focus mainly on current research findings to summarize and update the findings gathered from diverse areas of study. Based on these findings, we attempt to extend the role of CD38 in the context of therapy of solid tumors and expand the role of the molecule from a simple marker to an immunomodulator.

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