Biological Sciences

Transcription

Transcription is the process by which genetic information encoded in DNA is copied into RNA. This process is essential for gene expression and protein synthesis in living organisms. During transcription, an enzyme called RNA polymerase binds to a specific region of the DNA and synthesizes a complementary RNA molecule based on the DNA template.

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  • Book cover image for: Chemistry and Biology of Non-canonical Nucleic Acids
    • Naoki Sugimoto(Author)
    • 2021(Publication Date)
    • Wiley-VCH
      (Publisher)
    6 Transcription The main points of the learning Learn how Transcription works. Study how Transcription is perturbed depending on DNA and RNA sequences. Understand how Transcription is regulated by change of chemical environments. 6.1 Introduction Transcription is the process by which the information in a strand of DNA is copied into a new RNA molecule including messenger RNA (mRNA) by an RNA polymerase enzyme. During Transcription, a DNA sequence is read by the RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. Transcription factors can bind to specific DNA sequences called enhancer and promoter sequences in order to recruit RNA polymerase to an appropriate Transcription site. Then the RNA polymerase begins RNA synthesis by matching complementary bases to the original DNA strand. The RNA molecule is elongated, and, once the strand is completely synthesized, Transcription is terminated. The newly formed RNA copies of the gene are used for protein synthesis during the process of translation. This Transcription is highly regulated during both initiation and elongation [ 1 ]. Although fidelity of Transcription elongation is critical for maintaining the accurate flow of genetic information, Transcription elongation in cells and in vitro can be interrupted by certain sequences or structures [ 2 ]. Therefore, it is important to understand the effect of non-canonical DNAs on the Transcription process. In this chapter, the roles of non-canonical DNAs during Transcription are introduced with comparison of the difference from those of the canonical duplex
  • Book cover image for: Introduction to Genomic Signal Processing with Control
    • Aniruddha Datta, Edward R. Dougherty(Authors)
    • 2018(Publication Date)
    • CRC Press
      (Publisher)
    When a gene is being transcribed, it is said to be expressed or turned ON . The usual flow of genetic information is from DNA to RNA to protein. All cells, from the simplest bacteria to complex organisms such as humans, express their genetic information in this way. The principle is so fundamental to all of life that it is referred to as the central dogma of molecular biology . The use of an RNA intermediate makes it possible to more rapidly pro-duce larger amounts of a particular protein than would have otherwise been possible. This is because many identical RNA copies can be made from the same gene and each RNA copy can be used to simultaneously produce many identical protein molecules. By controlling the efficiency of Transcription and translation of the different genes, a cell can produce small amounts of some proteins and large amounts of others. In addition, a cell can change gene ex-pression in response to the temporally changing needs for a particular protein. 63 64 Introduction to Genomic Signal Processing with Control C C C C C C G G G G G G G G C A A U U A A A A U U U U U U U U G A A A A A U U U U U G C U U A G G G G G G G G G G C C U A U FIGURE 6.1 A single-stranded RNA molecule assuming a three-dimensional structure. 6.1 Transcription During Transcription, the cell copies the required part of the DNA sequence into a nucleotide sequence of RNA. As pointed out in Chapter 2, RNA differs chemically from DNA in two aspects: (1) The nucleotides in RNA are ribonucleotides , that is, they contain the sugar ribose instead of the sugar deoxyribose that is present in DNA; and (2) DNA contains the bases A, G, C and T while RNA contains the bases A, G, C and U. Since U pairs with A, the complementary base-pairing properties described in the last chapter for DNA apply also to RNA.
  • Book cover image for: Gene Transcription
    eBook - PDF

    Gene Transcription

    Mechanisms and Control

    All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the copyright owner. A catalogue record for this title is available from the British Library ISBN 0-632-04888-3 Library of Congress Cataloging-in-publication Data White Robert, J., 1963– Gene Transcription : mechanisms and control / Robert J. White. p. cm. Includes index. ISBN 0–632–04888–3 1. Genetic Transcription. 2. Genetic Transcription—Regulation. I. Title. QH450.2.W48 2000 572.8 ′ 845—dc21 00–040330 Contents Preface, vii Abbreviations, ix 1 Introduction, 1 2 The Nuclear RNA Polymerases, 17 3 DNA Recognition by Transcription Factors, 25 4 Basal Transcription by RNA Polymerase II, 50 5 Activating RNA Polymerase II Transcription, 72 6 Transcription by RNA Polymerase I, 102 7 Transcription by RNA Polymerase III, 113 8 The Influence of Chromatin on Transcription, 130 9 Controlling Transcription Factor Production, 169 10 Regulation of Transcription Factor Localization, 181 11 Regulation of Transcription Factor Activity, 200 12 Cell Cycle Regulation of Transcription, 224 13 Interactions Between Transcription and Other Nuclear Processes, 242 14 Transcription Factors and Development, 255 Index, 267 v Preface Transcription is an essential process which is required for abstract genetic information to become physical reality. As such it is fundamental to every living organism. It impinges upon all biological processes, such as growth, development and the ability to respond to environmental circumstances. Defects in Transcription are known to characterise the majority of human diseases. Given these truths, it is clear that any serious student of the life sciences must have some familiarity with the principles of Transcription.
  • Book cover image for: Mechanisms in Transcriptional Regulation
    Although the pathway from a gene to a mature protein can be regu-lated at any step, the most efficient way to regulate gene expression is to modulate the first step in the pathway since this avoids the costly syn-thesis of unneeded RNA. Organisms therefore produce an immense set of catalytic and regulatory factors dedicated to the task of transcribing genes in an intricately controlled manner. This chapter will introduce the components of this machinery and discuss the extent to which these com-ponents have been conserved during the course of evolution. At the same time, readers will become acquainted with some of the vocabulary needed to appreciate the exploration of the Transcriptional machinery presented in Chapters 2 through 7. 1.2 THE VOCABULARY OF Transcription Readers of this book should have had some previous exposure to most of the terms given in bold face in this section, and to basic ideas about pro-teins and nucleic acids through a college level course in biochemistry or molecular biology. Other important terms defined in this section, to which readers may or may not have previous exposure, will be given in italics. 1.2.1 RNA biogenesis Transcription , the first step in RNA biogenesis , is the DNA template-dependent synthesis of RNA, a process that is catalyzed by RNA poly-merases . Special DNA sequences termed promoters , which are found near the beginning of each transcribed region, direct these enzymes to initiate Transcription. Transcriptional initiation is followed by Transcriptional elongation , during which polymerase moves along the DNA, catalyzing the template-directed joining of nucleotides via phosphoester linkages to form a full-length primary transcript that is complementary in sequence to one of the DNA strands (the “template strand”). Elongation is, in turn, fol-lowed by Transcriptional termination , in which the polymerase encounters a termination signal triggering the release of both the transcript and the DNA from the polymerase.
  • Book cover image for: Fundamentals of Molecular Structural Biology
    Chapter 9

    Transcription

    Abstract

    Chapter 5 has introduced the macromolecules present in a cell. We have learnt that one of the macromolecules, DNA, carries the genetic information. In this chapter, we shall address the question as to how the genetic information is transferred from DNA to another macromolecule, RNA, in a process called Transcription. We shall see that Transcription is an outcome of the interaction between an enzyme called RNA polymerase (RNAP) and the DNA. Therefore, specific structural features of these two macromolecules will be considered to explain the interaction, and thus, understand the mechanism of Transcription, first in bacteria and then in eukaryotes. Further, we shall see that RNAP-DNA interaction is facilitated or impeded by other molecules in the cell. Pertinent structural features of some of these facilitators and inhibitors will also be considered to understand how the process of Transcription is regulated.

    Keywords

    Macromolecule; DNA; RNA; RNA polymerase; Promoter; Terminator; Transcription factor; Mediator; Activator; Repressor
    Chapter 5 has introduced the macromolecules of a cell—their structures and functions. Further, we have seen in the previous chapter how one of the macromolecules, DNA, that carries the genetic information of the cell is replicated. This chapter will address the question as to how this genetic information is transferred from DNA to another macromolecule, RNA, in a process called Transcription.

    9.1 Basic requirements for Transcription

    In a sense Transcription is similar to DNA replication—both involve the synthesis of a new strand of nucleic acid. However, in the case of Transcription, the new strand is synthesized by the addition of ribonucleotides, and not deoxyribonucleotides.
    Further, like DNA replication, the assembly of ribonucleotides in Transcription is not random; it is also directed by a DNA template strand. Nevertheless, in contrast to replication where the entire genome is copied once, and only once, in every cell division, Transcription copies only specific segments of the genome (genes) and can generate one to several thousand copies from a given segment. Even in such case, the DNA segment needs to be unwound and the bases unpaired so that nucleotide incorporation can proceed in accordance with the principle of base complementarity. One more distinguishing feature is that, unlike replication, in Transcription the RNA product does not remain base-paired with the template.
  • Book cover image for: Molecular Biology
    eBook - ePub
    • David P. Clark(Author)
    • 2009(Publication Date)
    • Academic Cell
      (Publisher)
    messenger RNA , or mRNA. Since the great majority of genes encode proteins, we will deal with these genes first.
    DNA “merely” stores genetic information. Putting the information to use requires RNA and (usually) protein.
    Messenger RNA carries the information for making proteins from the genes to the cytoplasm.
    For a gene to be transcribed, the DNA, which is double stranded, must first be pulled apart temporarily, as shown in Figure 6.01 . Then, RNA is made by RNA polymerase . This enzyme binds to the DNA at the start of a gene and opens the double helix. Finally, it manufactures an RNA molecule.
    Figure 6.01 Transcription in Its Simplest Form The two strands of the DNA to be transcribed are separated locally. The top strand serves as a template for building a new RNA molecule.
    The sequence of the RNA message is complementary to the template strand of the DNA from which it is synthesized. Apart from the replacement of thymine in DNA with uracil in RNA, this means that the sequence of the new RNA molecule is identical to the sequence of the coding strand of DNA; that is, the strand not actually used as a template during Transcription. Note that RNA, like DNA, is synthesized in the 5′-to 3′- direction (Fig. 6.02 ). Other names for the template strand are the non-coding or anti-sense strand; other names for the coding strand are non-template or sense strand. Only one of the strands of DNA is copied in any given transcribed region. [But note that the two different strands of the DNA may each be used as templates in different regions of the chromosome.]
    Figure 6.02 Naming the Basic Components Involved in Transcription
  • Book cover image for: The Human Genome
    eBook - ePub
    • Julia E. Richards, R. Scott Hawley(Authors)
    • 2010(Publication Date)
    • Academic Press
      (Publisher)
    Chapter 3. The Central Dogma of Molecular Biology How Cells Orchestrate the Use of Genetic Information
    Outline
    3.1 What Is RNA?84
    Permanent DNA and Temporary RNA Copies84
    Single-Stranded and Mixed-Stranded RNA87
    3.2 What Is RNA For?87
    3.3 Transcription of RNA89
    The Process of Transcription89
    3.4 Orchestrating Expression91
    The Concept of a Promoter92
    Regulators93
    Cis and Trans93
    3.5 Monitoring Gene Expression95
    RT-PCR: One Gene at a Time95
    Northern Blots: One Gene at a Time95
    Sequencing the Complete Transcriptome96
    Microarrays96
    3.6 Interaction of Transcription Factors98
    An Example of Two Regulatory Factors That Play a Critical Role in the Eye98
    Enhancers – Another Level of Regulation100
    RNA Turnover101
    3.7 Inducible Genes102
    Hormones103
    3.8 Epigenetic Control of Gene Expression104
    3.9 What Constitutes Normal?106
    The Problem with Diagnosing an Inducible Phenotype107
    Induction and Gene Regulation108
    So What or Who Is Normal Anyway?109
  • Book cover image for: Clinical Precision Medicine
    eBook - ePub
    • Judy S. Crabtree(Author)
    • 2019(Publication Date)
    • Academic Press
      (Publisher)
    An equally complex network of regulation controls gene expression or the process by which the blueprint information stored in an individual's DNA is converted into these functional proteins. Because of this complexity, small variations or alterations at any step in the conversion of DNA into protein may have significant outcomes that contribute to the development of the diseased state. More importantly, although individuals may have what appears to be an identical pathological presentation of a disease, many times the underlying genetic alterations that led to the development of this disease may be different, which could greatly affect their responses to therapy. Therefore, it is important to understand the molecular genetics of gene expression to better understand how the treatments used in the clinic are based solidly in the molecular mechanisms of the disease. In the late 1950s, Francis Crick proposed what would become known as the central dogma of molecular biology to describe the flow of gene expression from DNA through RNA and into protein (Fig. 2.1). In this central dogma, DNA serves as the template for the duplication of itself through a process called replication. The DNA also serves as the template for the production of the various forms of RNA (messenger RNA [mRNA], transfer RNA [tRNA], ribosomal RNA [rRNA], and microRNA [miRNA]) through a process called Transcription. Finally, the mRNA serves as the template for the production of protein, which it does with the assistance of tRNA and rRNA, through the process called translation
  • Book cover image for: Biochemistry of Signal Transduction and Regulation
    • Gerhard Krauss(Author)
    • 2014(Publication Date)
    • Wiley-VCH
      (Publisher)
    4 The Regulation of Gene Expression

    4.1 The Basic Steps of Gene Expression

    The transfer of genetic information from the level of the nucleic acid sequence of a gene to the level of the amino acid sequence of a protein or to the nucleotide sequence of RNA is termed gene expression. In eukaryotes, gene expression includes the following steps:
    • Transcription: the formation of a primary transcript, the pre-mRNA.
    • Conversion of the pre-mRNA into the mature mRNA: this includes processing, splicing, and transport from the nucleus to the cytosol.
    • Translation: synthesis of the protein on the ribosome.
    The expression of genes follows a tissue- and cell-specific pattern, which determines the function and morphology of a cell. In addition, all development and differentiation events are characterized by a variable pattern of gene expression. The regulation of gene expression thus plays a central role in the development and function of an organism. Because of the multitude of individual processes which are involved in gene expression, there are many potential regulatory sites (Figure 4.1 ).
    Figure 4.1
    Levels of regulation of eukaryotic gene expression.

    4.1.1 Regulation of Transcription

    At the level of Transcription, it can be determined whether a gene is transcribed at a given point in time. The chromatin structure plays a decisive role in this regulation, and chromatin structures exist that can effectively inhibit Transcription and shut down a gene. This “silencing” of genes can be either transient or permanent, and is generally observed in development and differentiation processes. The regulated Transcription of genes requires as an essential step the reorganization and modification of the chromatin, which is a prerequisite for the initiation of Transcription.
  • Book cover image for: Fundamental Aspects of DNA Replication
    • Jelena Kuši?-Tišma, Jelena Kušić-Tišma, Jelena Kušić-Tišma(Authors)
    • 2011(Publication Date)
    • IntechOpen
      (Publisher)
    16 Relations Between Replication and Transcription Daniel Castro-Roa and Nikolay Zenkin Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences Newcastle University, Newcastle upon Tyne United Kingdom 1. Introduction In the cell, RNA polymerase (RNAP) and the replisome share the same template DNA for their respective functions. The rate of replication is typically 20 times faster than Transcription and six or more replication forks may be present at the same time on the chromosome (Gotta et al. 1991; Hirose et al. 1983). This implies that collisions between the two machineries are inevitable. In this chapter we will discuss the recent findings on the outcome of collisions between Transcription and replication and their consequences, as well as cooperation between the two machineries. 2. Stability of RNA polymerase complexes with nucleic acids In all living organisms Transcription, the first step in gene expression, is accomplished by multisubunit RNAP. RNAP is highly evolutionary conserved, both structurally and functionally, in all three domains of life. Although there are differences in the mechanisms of initiation and regulation of Transcription, mechanisms of catalysis are remarkably similar in all living organisms. Fully functional eukaryotic and archeal models involve 12-14 subunits (depending on the polymerase type and organism) with a total molecular weight greater than 500 kDa (Cramer et al. 2001). The simplified versions found in bacteria are composed of five subunits (subunits composition 2 α , β ’, β and ω ) with a molecular mass of approximately 400 kDa. Transcription is a cyclic pathway roughly composed of three steps: initiation, elongation and termination. RNAP is a flexible machine able to adopt different states required for various Transcription stages and the mode and stability of binding of the enzyme to DNA at these stages are different.
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