The RNA World” Mean to “The Origin of Life”?
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Glossary - Cellbiology
1 Glossary - Cellbiology Blotting: (Blot Analysis) Widely used biochemical technique for detecting the presence of specific macromolecules (proteins, mRNAs, or DNA sequences) in a mixture. A sample first is separated on an agarose or polyacrylamide gel usually under denaturing conditions; the separated components are transferred (blotting) to a nitrocellulose sheet, which is exposed to a radiolabeled molecule that specifically binds to the macromolecule of interest, and then subjected to autoradiography. Northern B.: mRNAs are detected with a complementary DNA; Southern B.: DNA restriction fragments are detected with complementary nucleotide sequences; Western B.: Proteins are detected by specific antibodies. Cell: The fundamental unit of living organisms. Cells are bounded by a lipid-containing plasma membrane, containing the central nucleus, and the cytoplasm. Cells are generally capable of independent reproduction. More complex cells like Eukaryotes have various compartments (organelles) where special tasks essential for the survival of the cell take place. Cytoplasm: Viscous contents of a cell that are contained within the plasma membrane but, in eukaryotic cells, outside the nucleus. The part of the cytoplasm not contained in any organelle is called the Cytosol. Cytoskeleton: (Gk. ) Three dimensional network of fibrous elements, allowing precisely regulated movements of cell parts, transport organelles, and help to maintain a cell’s shape. • Actin filament: (Microfilaments) Ubiquitous eukaryotic cytoskeletal proteins (one end is attached to the cell-cortex) of two “twisted“ actin monomers; are important in the structural support and movement of cells. Each actin filament (F-actin) consists of two strands of globular subunits (G-Actin) wrapped around each other to form a polarized unit (high ionic cytoplasm lead to the formation of AF, whereas low ion-concentration disassembles AF). -
Building Blocks That Fall from the Sky
Building blocks that fall from the sky How did life on Earth begin? Scientists from the “Heidelberg Initiative for the Origin of Life” have set about answering this truly existential question. Indeed, they are going one step further and examining the conditions under which life can emerge. The initiative was founded by Thomas Henning, Director at the Max Planck Institute for Astronomy in Heidelberg, and brings together researchers from chemistry, physics and the geological and biological sciences. 18 MaxPlanckResearch 3 | 18 FOCUS_The Origin of Life TEXT THOMAS BUEHRKE he great questions of our exis- However, recent developments are The initiative was triggered by the dis- tence are the ones that fasci- forcing researchers to break down this covery of an ever greater number of nate us the most: how did the specialization and combine different rocky planets orbiting around stars oth- universe evolve, and how did disciplines. “That’s what we’re trying er than the Sun. “We now know that Earth form and life begin? to do with the Heidelberg Initiative terrestrial planets of this kind are more DoesT life exist anywhere else, or are we for the Origins of Life, which was commonplace than the Jupiter-like gas alone in the vastness of space? By ap- founded three years ago,” says Thom- giants we identified initially,” says Hen- proaching these puzzles from various as Henning. HIFOL, as the initiative’s ning. Accordingly, our Milky Way alone angles, scientists can answer different as- name is abbreviated, not only incor- is home to billions of rocky planets, pects of this question. -
Comparison of the Effects on Mrna and Mirna Stability Arian Aryani and Bernd Denecke*
Aryani and Denecke BMC Research Notes (2015) 8:164 DOI 10.1186/s13104-015-1114-z RESEARCH ARTICLE Open Access In vitro application of ribonucleases: comparison of the effects on mRNA and miRNA stability Arian Aryani and Bernd Denecke* Abstract Background: MicroRNA has become important in a wide range of research interests. Due to the increasing number of known microRNAs, these molecules are likely to be increasingly seen as a new class of biomarkers. This is driven by the fact that microRNAs are relatively stable when circulating in the plasma. Despite extensive analysis of mechanisms involved in microRNA processing, relatively little is known about the in vitro decay of microRNAs under defined conditions or about the relative stabilities of mRNAs and microRNAs. Methods: In this in vitro study, equal amounts of total RNA of identical RNA pools were treated with different ribonucleases under defined conditions. Degradation of total RNA was assessed using microfluidic analysis mainly based on ribosomal RNA. To evaluate the influence of the specific RNases on the different classes of RNA (ribosomal RNA, mRNA, miRNA) ribosomal RNA as well as a pattern of specific mRNAs and miRNAs was quantified using RT-qPCR assays. By comparison to the untreated control sample the ribonuclease-specific degradation grade depending on the RNA class was determined. Results: In the present in vitro study we have investigated the stabilities of mRNA and microRNA with respect to the influence of ribonucleases used in laboratory practice. Total RNA was treated with specific ribonucleases and the decay of different kinds of RNA was analysed by RT-qPCR and miniaturized gel electrophoresis. -
(12) Patent Application Publication (10) Pub. No.: US 2013/0203610 A1 Meller Et Al
US 20130203610A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0203610 A1 Meller et al. (43) Pub. Date: Aug. 8, 2013 (54) TOOLS AND METHOD FOR NANOPORES Related U.S. Application Data UNZIPPING-DEPENDENT NUCLECACID (60) Provisional application No. 61/318,872, filed on Mar. SEQUENCING 30, 2010. (75) Inventors: Amit Meller, Brookline, MA (US); Alon Publication Classification Singer, Brighton, MA (US) (51) Int. Cl. (73) Assignee: TRUSTEES OF BOSTON CI2O I/68 (2006.01) UNIVERSITY, Boston, MA (US) (52) U.S. Cl. CPC .................................... CI2O I/6874 (2013.01) (21) Appl. No.: 13/638,455 USPC ................................................. 506/6:506/16 (57) ABSTRACT (22) PCT Filed: Mar. 30, 2011 Provided herein is a library that comprises a plurality of molecular beacons (MBs), each MB having a detectable (86). PCT No.: PCT/US2O11AO3O430 label, a detectable label blocker and a modifier group. The S371 (c)(1), library is used in conjunction with nanopore unzipping-de (2), (4) Date: Apr. 17, 2013 pendent sequencing of nucleic acids. Patent Application Publication Aug. 8, 2013 Sheet 1 of 18 US 2013/020361.0 A1 . N s Patent Application Publication Aug. 8, 2013 Sheet 2 of 18 US 2013/020361.0 A1 I’9IAI ::::::::::: Dº3.modoueN Patent Application Publication Aug. 8, 2013 Sheet 3 of 18 US 2013/020361.0 A1 Z’9IAI ~~~~~~~~~);........ Patent Application Publication Aug. 8, 2013 Sheet 4 of 18 US 2013/020361.0 A1 s :·.{-zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz iii. 9 iii.338 lii &S Patent Application Publication Aug. 8, 2013 Sheet 5 of 18 US 2013/020361.0 A1 s r Patent Application Publication Aug. -
Peptide Analogue of Glycol Nucleic Acid†
Communications to the Editor Bull. Korean Chem. Soc. 2011, Vol. 32, No. 8 2863 DOI 10.5012/bkcs.2011.32.8.2863 γ3PNA: Peptide Analogue of Glycol Nucleic Acid† Taedong Ok, Joohee Lee, and Hee-Seung Lee* Molecular-Level Interface Research Center, Department of Chemistry, KAIST, Daejeon 305-701 *E-mail: [email protected] Received February 7, 2011, Accepted February 9, 2011 Key Words : Peptide nucleic acids, GNA In the research of the chemical etiology of nucleic acid chemical yield were obtained with Mmt for γ3C and γ3G, Boc structure, the studies from Eschenmoser group1 and Nielsen for γ3A, respectively. In addition, the order of reactions at the group2 have demonstrated that the Watson-Crick base pairing initial steps turned out to be important for efficient synthesis. can be supported by various backbone derivatives. Inspired by For example, in case of γ3C, the protection of the amino groups the groundbreaking results, other researchers have devoted should be prior to the substitution reaction, whereas the other their attention to finding artificial nucleic acids that can form route worked better for the purine monomers (γ3A and γ3G). duplexes, in which both synthetic accessibility and new The detailed synthetic procedures are summarized in characteristics for potential therapeutic (or diagnostic) use are Scheme 1. The common intermediate bromide 1 was easily desirable aims.3 In this context, GNA (glycol nucleic acid, prepared from (S)-epichlorohydrin (> 99%ee) in three steps Figure 1A) is a promising artificial nucleic acid because it is (34% overall yield).6,7 For the synthesis of γ3A, the bromide 1 structurally very simple with a high atom economy and was reacted with unprotected adenine base in the presence of forms a duplex by Watson-Crick base pairing.4 sodium hydride in DMF for 48 hr at room temperature. -
Prebiological Evolution and the Metabolic Origins of Life
Prebiological Evolution and the Andrew J. Pratt* Metabolic Origins of Life University of Canterbury Keywords Abiogenesis, origin of life, metabolism, hydrothermal, iron Abstract The chemoton model of cells posits three subsystems: metabolism, compartmentalization, and information. A specific model for the prebiological evolution of a reproducing system with rudimentary versions of these three interdependent subsystems is presented. This is based on the initial emergence and reproduction of autocatalytic networks in hydrothermal microcompartments containing iron sulfide. The driving force for life was catalysis of the dissipation of the intrinsic redox gradient of the planet. The codependence of life on iron and phosphate provides chemical constraints on the ordering of prebiological evolution. The initial protometabolism was based on positive feedback loops associated with in situ carbon fixation in which the initial protometabolites modified the catalytic capacity and mobility of metal-based catalysts, especially iron-sulfur centers. A number of selection mechanisms, including catalytic efficiency and specificity, hydrolytic stability, and selective solubilization, are proposed as key determinants for autocatalytic reproduction exploited in protometabolic evolution. This evolutionary process led from autocatalytic networks within preexisting compartments to discrete, reproducing, mobile vesicular protocells with the capacity to use soluble sugar phosphates and hence the opportunity to develop nucleic acids. Fidelity of information transfer in the reproduction of these increasingly complex autocatalytic networks is a key selection pressure in prebiological evolution that eventually leads to the selection of nucleic acids as a digital information subsystem and hence the emergence of fully functional chemotons capable of Darwinian evolution. 1 Introduction: Chemoton Subsystems and Evolutionary Pathways Living cells are autocatalytic entities that harness redox energy via the selective catalysis of biochemical transformations. -
Solar System Simulator NASA SUMMER of INNOVATION
National Aeronautics and Space Administration Solar System Simulator NASA SUMMER OF INNOVATION UNIT Earth and Space Science – Year of the Solar System DESCRIPTION This online software generates views of GRADE LEVELS the bodies of our planetary system at any th th 7 – 9 date from any artificial or natural point of observation. CONNECTION TO CURRICULUM Science and technology OBJECTIVES TEACHER PREPARATION TIME Students will: 1 hour • Investigate how to determine the relative position of the sun, LESSON TIME NEEDED planets, and a number of 30 minutes Complexity: Basic planetary spacecraft using a simple web-based program • Explore how planets change their position in space over time NATIONAL STANDARDS National Science Education Standards (NSTA) Science and Technology Standards • Abilities of technological design • Understanding about science and technology Earth and Space Science • Earth in the solar system • Objects in the sky Common Core State Standards for Mathematics (NCTM) Number and Operations in Base Ten • Perform operations with multi-digit whole numbers and with decimals to hundredths Operations and Algebraic Thinking • Generate and analyze patterns ISTE NETS and Performance Indicators for Students (ISTE) Creativity and Innovation • Use models and simulations to explore complex systems and issues. Technology Operations and Concepts • Understand and use technology systems Aerospace Education Services Project MANAGEMENT MATERIALS Take time to practice with this software. While simple, it offers a • Computer with Internet variety of views with which to become familiar. access On the simulator homepage, a FIELD OF VIEW of 2 will show the inner solar system very nicely. It will be difficult to see the position of ALL the planets at one time. -
Exploring the Structure of Long Non-Coding Rnas, J
IMF YJMBI-63988; No. of pages: 15; 4C: 3, 4, 7, 8, 10 1 2 Rise of the RNA Machines: Exploring the Structure of 3 Long Non-Coding RNAs 4 Irina V. Novikova, Scott P. Hennelly, Chang-Shung Tung and Karissa Y. Sanbonmatsu Q15 6 Los Alamos National Laboratory, Los Alamos, NM 87545, USA 7 Correspondence to Karissa Y. Sanbonmatsu: [email protected] 8 http://dx.doi.org/10.1016/j.jmb.2013.02.030 9 Edited by A. Pyle 1011 12 Abstract 13 Novel, profound and unexpected roles of long non-coding RNAs (lncRNAs) are emerging in critical aspects of 14 gene regulation. Thousands of lncRNAs have been recently discovered in a wide range of mammalian 15 systems, related to development, epigenetics, cancer, brain function and hereditary disease. The structural 16 biology of these lncRNAs presents a brave new RNA world, which may contain a diverse zoo of new 17 architectures and mechanisms. While structural studies of lncRNAs are in their infancy, we describe existing 18 structural data for lncRNAs, as well as crystallographic studies of other RNA machines and their implications 19 for lncRNAs. We also discuss the importance of dynamics in RNA machine mechanism. Determining 20 commonalities between lncRNA systems will help elucidate the evolution and mechanistic role of lncRNAs in 21 disease, creating a structural framework necessary to pursue lncRNA-based therapeutics. 22 © 2013 Published by Elsevier Ltd. 24 23 25 Introduction rather than the exception in the case of eukaryotic 50 organisms. 51 26 RNA is primarily known as an intermediary in gene LncRNAs are defined by the following: (i) lack of 52 11 27 expression between DNA and proteins. -
How Might a Pre-Biotic Ribozyme Catalyze RNA Assembly in an RNA World?
Science Highlight – April 2007 How Might a Pre-biotic Ribozyme Catalyze RNA Assembly in an RNA World? Which came first, nucleic acids or proteins? This question is molecular biology's version of the "chicken-or-the-egg" riddle. Genes made of nucleic acids (DNA or RNA) contain the instructions for making proteins, but enzymes made of proteins are needed to replicate genes. For those who try to understand how life origi- nated, this once seemed an intractable paradox. The discovery 25 years ago that RNA can be enzymatic permits us to speculate that pre-biotic self-replicating molecules may have been RNAs (1,2). This is known as the "RNA World" hypothesis, and with the discovery of RNA catalysis, it is now possible to imagine a prebiotic The L1 Ligase ribozyme at the moment 'RNA World' (or even one populated by early life forms) of bond creation. in which self-replicating ribozymes (RNA-based enzymes that possess the catalytic ability to copy themselves) accomplished both tasks, thus avoiding the potential “chicken-or-the-egg” conundrum (3). But there's a catch. In order to copy RNA, fragments or monomers that have 5'-triphosphates must be ligated together. This is true for modern polymerases, and is also the most likely mechanism by which a ribozyme self-replicase in an RNA World might function. Yet no one has found a modern natural ribozyme that catalyze this The RNA nucleotide triphosphate ligation reaction required reaction (pictured right). for RNA polymerization and self-replication. RNA in vitro evolution and selection has however enabled several research groups to discover RNA sequences that can in fact cata- lyze the required chemical reaction (shown above) for 5'-triphos- phate RNA fragment ligation, and one group has even produced a primitive but functional RNA-based RNA polymerase ribozyme (4). -
RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases
G C A T T A C G G C A T genes Review RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases Amber Willbanks, Shaun Wood and Jason X. Cheng * Department of Pathology, Hematopathology Section, University of Chicago, Chicago, IL 60637, USA; [email protected] (A.W.); [email protected] (S.W.) * Correspondence: [email protected] Abstract: Chromatin structure plays an essential role in eukaryotic gene expression and cell identity. Traditionally, DNA and histone modifications have been the focus of chromatin regulation; however, recent molecular and imaging studies have revealed an intimate connection between RNA epigenetics and chromatin structure. Accumulating evidence suggests that RNA serves as the interplay between chromatin and the transcription and splicing machineries within the cell. Additionally, epigenetic modifications of nascent RNAs fine-tune these interactions to regulate gene expression at the co- and post-transcriptional levels in normal cell development and human diseases. This review will provide an overview of recent advances in the emerging field of RNA epigenetics, specifically the role of RNA modifications and RNA modifying proteins in chromatin remodeling, transcription activation and RNA processing, as well as translational implications in human diseases. Keywords: 5’ cap (5’ cap); 7-methylguanosine (m7G); R-loops; N6-methyladenosine (m6A); RNA editing; A-to-I; C-to-U; 2’-O-methylation (Nm); 5-methylcytosine (m5C); NOL1/NOP2/sun domain Citation: Willbanks, A.; Wood, S.; (NSUN); MYC Cheng, J.X. RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases. Genes 2021, 12, 627. -
A Tetracycline-Dependent Ribozyme Switch Allows Conditional Induction of Gene Expression in Caenorhabditis Elegans
ARTICLE https://doi.org/10.1038/s41467-019-08412-w OPEN A tetracycline-dependent ribozyme switch allows conditional induction of gene expression in Caenorhabditis elegans Lena A. Wurmthaler1,2, Monika Sack1,2, Karina Gense2,3, Jörg S. Hartig1,2 & Martin Gamerdinger2,3 The nematode Caenorhabditis elegans represents an important research model. Convenient methods for conditional induction of gene expression in this organism are not available. Here 1234567890():,; we describe tetracycline-dependent ribozymes as versatile RNA-based genetic switches in C. elegans. Ribozyme insertion into the 3’-UTR converts any gene of interest into a tetracycline- inducible gene allowing temporal and, by using tissue-selective promoters, spatial control of expression in all developmental stages of the worm. Using the ribozyme switches we established inducible C. elegans polyglutamine Huntington’s disease models exhibiting ligand- controlled polyQ-huntingtin expression, inclusion body formation, and toxicity. Our approach circumvents the complicated expression of regulatory proteins. Moreover, only little coding space is necessary and natural promoters can be utilized. With these advantages tetracycline-dependent ribozymes significantly expand the genetic toolbox for C. elegans. 1 Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany. 2 Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz, 78457 Konstanz, Germany. 3 Department of Biology, University of Konstanz, 78457 Konstanz, Germany. Correspondence and requests for materials should be addressed to J.S.H. (email: [email protected]) or to M.G. (email: [email protected]) NATURE COMMUNICATIONS | (2019) 10:491 | https://doi.org/10.1038/s41467-019-08412-w | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-08412-w nducible regulatory systems are very powerful research tools to single A-to-G point mutation in the catalytic core of the HHR9 Iinvestigate the cellular function of individual genes. -
Genome-Wide Detection of Chromosomal Rearrangements, Indels, and Mutations in Circular Chromosomes by Short Read Sequencing
Downloaded from genome.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Method Genome-wide detection of chromosomal rearrangements, indels, and mutations in circular chromosomes by short read sequencing Ole Skovgaard,1,3 Mads Bak,2 Anders Løbner-Olesen,1 and Niels Tommerup2 1Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde, Denmark; 2Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark Whole-genome sequencing (WGS) with new short-read sequencing technologies has recently been applied for genome- wide identification of mutations. Genomic rearrangements have, however, often remained undetected by WGS, and additional analyses are required for their detection. Here, we have applied a combination of WGS and genome copy number analysis, for the identification of mutations that suppress the growth deficiency imposed by excessive initiations from the Escherichia coli origin of replication, oriC. The E. coli chromosome, like the majority of bacterial chromosomes, is circular, and DNA replication is initiated by assembling two replication complexes at the origin, oriC. These complexes then replicate the chromosome bidirectionally toward the terminus, ter. In a population of growing cells, this results in a copy number gradient, so that origin-proximal sequences are more frequent than origin-distal sequences. Major rearrangements in the chromosome are, therefore, readily identified by changes in copy number, i.e., certain sequences become over- or under-represented. Of the eight mutations analyzed in detail here, six were found to affect a single gene only, one was a large chromosomal inversion, and one was a large chromosomal duplication.