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Journal of Molecular Biology Jun 2016Transcription by RNA polymerase II (Pol II) is required to produce mRNAs and some noncoding RNAs (ncRNAs) within mammalian cells. This coordinated process is precisely... (Review)
Review
Transcription by RNA polymerase II (Pol II) is required to produce mRNAs and some noncoding RNAs (ncRNAs) within mammalian cells. This coordinated process is precisely regulated by multiple factors, including many recently discovered ncRNAs. In this perspective, we will discuss newly identified ncRNAs that facilitate DNA looping, regulate transcription factor binding, mediate promoter-proximal pausing of Pol II, and/or interact with Pol II to modulate transcription. Moreover, we will discuss new roles for ncRNAs, as well as a novel Pol II RNA-dependent RNA polymerase activity that regulates an ncRNA inhibitor of transcription. As the multifaceted nature of ncRNAs continues to be revealed, we believe that many more ncRNA species and functions will be discovered.
Topics: Animals; DNA; Humans; Mammals; Promoter Regions, Genetic; RNA Polymerase II; RNA, Untranslated; Transcription Factors; Transcription, Genetic
PubMed: 26920110
DOI: 10.1016/j.jmb.2016.02.019 -
Development, Growth & Differentiation Jan 2016In development, morphogenetic processes are strictly coordinated in time. Cells in a developing tissue would need mechanisms for time-keeping. One such time-keeping... (Review)
Review
In development, morphogenetic processes are strictly coordinated in time. Cells in a developing tissue would need mechanisms for time-keeping. One such time-keeping mechanism is to use oscillations of gene expression. Oscillatory gene expression can be generated by transcriptional/translational feedback loops, usually referred to as a genetic oscillator. In this review article, we discuss genetic oscillators in the presence of developmental processes such as cell division, cell movement and cell differentiation. We first introduce the gene regulatory network for generating a rhythm of gene expression. We then discuss how developmental processes influence genetic oscillators. Examples include vertebrate somitogenesis and neural progenitor cell differentiation, as well as the circadian clock for comparison. To understand the behaviors of genetic oscillators in development, it is necessary to consider both gene expression dynamics and cellular behaviors simultaneously. Theoretical modeling combined with live imaging at single-cell resolution will be a powerful tool to analyze genetic oscillators in development.
Topics: Animals; Biological Clocks; Cell Differentiation; Cell Division; Gene Expression Regulation, Developmental; Humans; Transcription, Genetic
PubMed: 26753997
DOI: 10.1111/dgd.12262 -
EMBO Reports Aug 2009Histone modifications are a crucial source of epigenetic control. SAGA (Spt-Ada-Gcn5 acetyltransferase) is a chromatin-modifying complex that contains two distinct... (Review)
Review
Histone modifications are a crucial source of epigenetic control. SAGA (Spt-Ada-Gcn5 acetyltransferase) is a chromatin-modifying complex that contains two distinct enzymatic activities, Gcn5 and Ubp8, through which it acetylates and deubiquitinates histone residues, respectively, thereby enforcing a pattern of modifications that is decisive in regulating gene expression. Here, I discuss the latest contributions to understanding the roles of the SAGA complex, highlighting the characterization of the SAGA-deubiquitination module, and emphasizing the functions newly ascribed to SAGA during transcription elongation and messenger-RNA export. These findings suggest that a crosstalk exists between chromatin remodelling, transcription and messenger-RNA export, which could constitute a checkpoint for accurate gene expression. I focus particularly on the new components of human SAGA, which was recently discovered and confirms the conservation of the SAGA complex throughout evolution.
Topics: Acetyltransferases; Animals; Chromatin Assembly and Disassembly; Endopeptidases; Humans; Models, Biological; Transcription, Genetic; p300-CBP Transcription Factors
PubMed: 19609321
DOI: 10.1038/embor.2009.168 -
Experimental Physiology Jan 2003Mitochondria are subcellular organelles, devoted mainly to energy production in the form of ATP, that contain their own genetic system. Mitochondrial DNA codifies a... (Review)
Review
Mitochondria are subcellular organelles, devoted mainly to energy production in the form of ATP, that contain their own genetic system. Mitochondrial DNA codifies a small, but essential number of polypeptides of the oxidative phosphorylation system. The mammalian mitochondrial genome is an example of extreme economy showing a compact gene organization. The coding sequences for two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and 13 polypeptides are contiguous and without introns. The tRNAs are regularly interspersed between the rRNA and protein-coding genes, playing a crucial role in RNA maturation from the polycistronic transcripts. A single major non-coding region, called the D-loop region, contains the main regulatory sequences for transcription and replication initiation. This genetic organization has its precise correspondence in the mode of expression and distinctive structural features of the RNAs. The basic mechanisms of mitochondrial DNA transcription and replication and the main cis-acting elements playing a role in both processes have been determined. Many trans-acting factors involved in mitochondrial gene expression, including the RNA and DNA polymerases, have been cloned or identified. However, the regulatory mechanisms participating in mitochondrial gene expression are still poorly understood. The interest to complete this knowledge is increased by the involvement of mitochondria in human diseases, in basic processes such as heat production, Ca(2+) homeostasis and apoptosis, and by their potential role in ageing and carcinogenesis.
Topics: Animals; DNA Replication; DNA, Mitochondrial; Gene Expression Regulation; Homeostasis; Humans; Mammals; Molecular Structure; RNA; RNA, Mitochondrial; Transcription, Genetic
PubMed: 12525854
DOI: 10.1113/eph8802514 -
The New Phytologist Feb 2018Contents Summary 1029 I. Introduction 1029 II. Convergence at the receptor 1030 III. Convergence at transcriptional hubs 1031 IV. Convergence involving clock components... (Review)
Review
Contents Summary 1029 I. Introduction 1029 II. Convergence at the receptor 1030 III. Convergence at transcriptional hubs 1031 IV. Convergence involving clock components 1033 V. Conclusions 1033 Acknowledgements 1033 References 1033 SUMMARY: The combined information provided by light and temperature cues helps to optimise plant body architecture and physiology. Plants possess elaborate systems to sense and respond to these stimuli. Simultaneous perception of light and temperature by dual receptors such as phytochrome B and phototropin leads to immediate signalling convergence. Conversely, cue asynchronies initiate separate pathways and the information of the earliest cue is stored, awaiting the arrival of the later cue to control transcription. Storage mechanisms can involve changes in the activity of selected clock components or epigenetic modifications, depending on the time delay between cues (hours, days or several months). We propose a conceptual framework in which the mechanisms of integration relate to the timing of cue sensing.
Topics: Biological Clocks; Light; Models, Biological; Receptors, Cell Surface; Temperature; Transcription, Genetic
PubMed: 29139132
DOI: 10.1111/nph.14890 -
Arthritis Research & Therapy Mar 2011Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from a loss of tolerance to multiple self antigens, and characterized by autoantibody production... (Review)
Review
Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from a loss of tolerance to multiple self antigens, and characterized by autoantibody production and inflammatory cell infiltration in target organs, such as the kidneys and brain. T cells are critical players in SLE pathophysiology as they regulate B cell responses and also infiltrate target tissues, leading to tissue damage. Abnormal signaling events link to defective gene transcription and altered cytokine production, contributing to the aberrant phenotype of T cells in SLE. Study of signaling and gene transcription abnormalities in SLE T cells has led to the identification of novel targets for therapy.
Topics: Humans; Lupus Erythematosus, Systemic; Signal Transduction; T-Lymphocytes; Transcription, Genetic
PubMed: 21457530
DOI: 10.1186/ar3251 -
Nature Reviews. Immunology Nov 2011Recent advances in technologies for genome- and proteome-scale measurements and perturbations promise to accelerate discovery in every aspect of biology and medicine.... (Review)
Review
Recent advances in technologies for genome- and proteome-scale measurements and perturbations promise to accelerate discovery in every aspect of biology and medicine. Although such rapid technological progress provides a tremendous opportunity, it also demands that we learn how to use these tools effectively. One application with great potential to enhance our understanding of biological systems is the unbiased reconstruction of genetic and molecular networks. Cells of the immune system provide a particularly useful model for developing and applying such approaches. Here, we review approaches for the reconstruction of signalling and transcriptional networks, with a focus on applications in the mammalian innate immune system.
Topics: Animals; Forecasting; Gene Expression Regulation; Genomics; Humans; Immune System; Immunity, Innate; Immunogenetic Phenomena; Immunogenetics; Mammals; Models, Immunological; Proteomics; Signal Transduction; Transcription, Genetic
PubMed: 22094988
DOI: 10.1038/nri3109 -
Molecules and Cells Apr 2001The large number of signaling pathways and regulatory proteins that affect transcription highlights a need for funneling of information since transcription of all... (Review)
Review
The large number of signaling pathways and regulatory proteins that affect transcription highlights a need for funneling of information since transcription of all protein encoding genes is executed by the same set of general transcription factors and RNA polymerase II. This demand is met by large protein complexes such as Mediator that interact with the basic RNA polymerase II machinery and thus adds diversity simply by increasing the surface that is exposed to the incoming signals. The recent description of Mediator-like complexes in metazoans identifies it as a key player in transcriptional regulation.
Topics: Animals; Fungal Proteins; Humans; Macromolecular Substances; Protein Subunits; RNA Polymerase II; Signal Transduction; Transcription, Genetic; Yeasts
PubMed: 11355691
DOI: No ID Found -
Genes & Development Aug 2019Genome replication involves dealing with obstacles that can result from DNA damage but also from chromatin alterations, topological stress, tightly bound proteins or... (Review)
Review
Genome replication involves dealing with obstacles that can result from DNA damage but also from chromatin alterations, topological stress, tightly bound proteins or non-B DNA structures such as R loops. Experimental evidence reveals that an engaged transcription machinery at the DNA can either enhance such obstacles or be an obstacle itself. Thus, transcription can become a potentially hazardous process promoting localized replication fork hindrance and stress, which would ultimately cause genome instability, a hallmark of cancer cells. Understanding the causes behind transcription-replication conflicts as well as how the cell resolves them to sustain genome integrity is the aim of this review.
Topics: DNA Replication; Genome; Genomic Instability; Humans; Neoplasms; Transcription Elongation, Genetic; Transcription, Genetic
PubMed: 31123061
DOI: 10.1101/gad.324517.119 -
Transcription 2018Sub1 was initially identified as a coactivator factor with a role during transcription initiation. However, over the last years, many evidences showed that it influences... (Review)
Review
Sub1 was initially identified as a coactivator factor with a role during transcription initiation. However, over the last years, many evidences showed that it influences processes downstream during mRNA biogenesis, such as elongation, termination, and RNAPII phosphorylation. The recent discover that Sub1 directly interacts with the RNAPII stalk adds new insights into how it achieves all these tasks.
Topics: DNA-Binding Proteins; Humans; RNA Polymerase II; Transcription Factors; Transcription Termination, Genetic; Transcription, Genetic
PubMed: 28853990
DOI: 10.1080/21541264.2017.1333558