The Evolution and Functions of Trna Modifications
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Identification and Codon Reading Properties of 5
Identification and codon reading properties of 5-cyanomethyl uridine, a new modified nucleoside found in the anticodon wobble position of mutant haloarchaeal isoleucine tRNAs The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Mandal, D., C. Kohrer, D. Su, I. R. Babu, C. T. Y. Chan, Y. Liu, D. Soll, et al. “Identification and Codon Reading Properties of 5- Cyanomethyl Uridine, a New Modified Nucleoside Found in the Anticodon Wobble Position of Mutant Haloarchaeal Isoleucine tRNAs.” RNA 20, no. 2 (December 16, 2013): 177–188. As Published http://dx.doi.org/10.1261/rna.042358.113 Publisher Cold Spring Harbor Laboratory Press/RNA Society Version Final published version Citable link http://hdl.handle.net/1721.1/91989 Terms of Use Creative Commons Attribution-Noncommerical Detailed Terms http://creativecommons.org/licenses/by-nc/3.0/ Downloaded from rnajournal.cshlp.org on April 3, 2014 - Published by Cold Spring Harbor Laboratory Press Identification and codon reading properties of 5-cyanomethyl uridine, a new modified nucleoside found in the anticodon wobble position of mutant haloarchaeal isoleucine tRNAs Debabrata Mandal, Caroline Köhrer, Dan Su, et al. RNA 2014 20: 177-188 originally published online December 16, 2013 Access the most recent version at doi:10.1261/rna.042358.113 Supplemental http://rnajournal.cshlp.org/content/suppl/2013/12/03/rna.042358.113.DC1.html Material References This article cites 38 articles, 17 of which can be accessed free at: http://rnajournal.cshlp.org/content/20/2/177.full.html#ref-list-1 Creative This article is distributed exclusively by the RNA Society for the first 12 months after the Commons full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). -
Characterization of a B. Subtilis Minor Isoleucine Trna Deduced from Tdna Having a Methionine Anticodon CAT1
J. Biochem. 119, 811-816 (1996) Characterization of a B. subtilis Minor Isoleucine tRNA Deduced from tDNA Having a Methionine Anticodon CAT1 Jitsuhiro Matsugi,2 Katsutoshi Murao, and Hisayuki Ishikura Laboratory of Chemistry, Jichi Medical School, 3311-1 Minamikawachi-machi, Tochigi 329-04 Received for publication, December 1, 1995 Bacillus subtilis, which belongs to Gram-positive eubacteria, has been predicted to have a minor isoleucine tRNA transcribed from the gene possessing the CAT anticodon, which corresponds to methionine. We isolated this tRNA and determined its sequence including modified nucleotides. Modified nucleotide analyses using TLC, UV, and FAB mass spectros copy revealed that the first letter of the anticodon is modified to lysidine [4-amino-2-(N6 - lysino)-1-ƒÀ-D-ribofuranosyl pyrimidine]. As a result, this tRNA agrees with the minor one predicted from the DNA sequence and is thought to decode the isoleucine codon AUA. Key words: Bacillus subtilis, FAB mass spectroscopy, lysidine, modified nucleotide, tRNA. In the codon table, isoleucine is assigned to three codons, lysidine in the wobble position can form a base pair only AUU, AUC, and AUA, but theoretically two kinds of with adenosine, not with guanosine, and consequently the anticodon (GAU and UAU) are sufficient to decode these minor tRNA11e can read only the AUA codon. At the same three codons. To decode the AUA codon, some organisms time, lysidine contributes to a change in charging specificity utilize a minor species of tRNA11e whose first letter of the from methionine to isoleucine (7). anticodon is a unique or an unknown modified nucleotide. In B. -
Us 2018 / 0353618 A1
US 20180353618A1 ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 /0353618 A1 Burkhardt et al. (43 ) Pub . Date : Dec . 13 , 2018 (54 ) HETEROLOGOUS UTR SEQUENCES FOR Publication Classification ENHANCED MRNA EXPRESSION (51 ) Int. Cl. A61K 48 / 00 ( 2006 .01 ) (71 ) Applicant : Moderna TX , Inc ., Cambridge , MA C12N 15 / 10 (2006 .01 ) (US ) C12N 15 /67 ( 2006 .01 ) (72 ) Inventors : David H . Burkhardt , Somerville , MA A61K 31 / 7115 ( 2006 .01 ) (US ) ; Romesh R . Subramanian , A61K 31 /712 ( 2006 .01 ) A61K 31 / 7125 (2006 . 01 ) Framingham , MA (US ) ; Christian A61P 1 / 16 ( 2006 .01 ) Cobaugh , Newton Highlands , MA (US ) A61P 31/ 14 (2006 .01 ) (52 ) U . S . CI. (73 ) Assignee : Moderna TX , Inc. , Cambridge , MA CPC . .. A61K 48 /0058 ( 2013 .01 ) ; C12N 15 / 1086 (US ) ( 2013 . 01 ) ; A61K 48 / 0066 ( 2013 .01 ) ; C12N 15 /67 ( 2013 .01 ) ; A61P 31 / 14 ( 2018 . 01 ) ; A61K ( 21 ) Appl . No . : 15 / 781, 827 31/ 712 (2013 .01 ) ; A61K 31/ 7125 ( 2013 .01 ) ; A61P 1 / 16 ( 2018 .01 ) ; A61K 31/ 7115 ( 22 ) PCT Filed : Dec . 9 , 2016 ( 2013 .01 ) ( 86 ) PCT No. : PCT/ US2016 / 065796 (57 ) ABSTRACT $ 371 ( c ) ( 1 ) , mRNAs containing an exogenous open reading frame (ORF ) ( 2 ) Date : flanked by a 5 ' untranslated region (UTR ) and a 3 ' UTR is Jun . 6 , 2018 provided , wherein the 5 ' and 3 ' UTRs are derived from a naturally abundant mRNA in a tissue . Also provided are Related U . S . Application Data methods for identifying the 5 ' and 3 ' UTRs, and methods for (60 ) Provisional application No . 62 / 265 , 233 , filed on Dec. making and using the mRNAs . -
WO 2017/112943 Al 29 June 2017 (29.06.2017) W P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/112943 Al 29 June 2017 (29.06.2017) W P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C07K 14/705 (2006.01) A61K 31/7088 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, C12N 15/12 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, (21) International Application Number: KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, PCT/US2016/068552 MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, (22) International Filing Date: NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, 23 December 2016 (23. 12.2016) RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, (25) Filing Language: English ZA, ZM, ZW. (26) Publication Language: English 4 Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 62/387,168 23 December 201 5 (23. 12.2015) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/290,413 2 February 2016 (02.02.2016) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: MODERNATX, INC. -
Life Without Trna[Superscript Ile]-Lysidine Synthetase: Translation of the Isoleucine Codon AUA in Bacillus Subtilis Lacking the Canonical Trna[Ile Over 2]
Life without tRNA[superscript Ile]-lysidine synthetase: translation of the isoleucine codon AUA in Bacillus subtilis lacking the canonical tRNA[Ile over 2] The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Kohrer, C., D. Mandal, K. W. Gaston, H. Grosjean, P. A. Limbach, and U. L. RajBhandary. “Life without tRNAIle-lysidine synthetase: translation of the isoleucine codon AUA in Bacillus subtilis lacking the canonical tRNA2Ile.” Nucleic Acids Research (November 4, 2013). As Published http://dx.doi.org/10.1093/nar/gkt1009 Publisher Oxford University Press Version Final published version Citable link http://hdl.handle.net/1721.1/83245 Detailed Terms http://creativecommons.org/licenses/by-nc/3.0/ Nucleic Acids Research Advance Access published November 14, 2013 Nucleic Acids Research, 2013, 1–12 doi:10.1093/nar/gkt1009 Life without tRNAIle-lysidine synthetase: translation of the isoleucine codon AUA in Bacillus subtilis Ile lacking the canonical tRNA2 Caroline Ko¨ hrer1, Debabrata Mandal1, Kirk W. Gaston2, Henri Grosjean3, Patrick A. Limbach2 and Uttam L. RajBhandary1,* 1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA, 2Department of Chemistry, Rieveschl Laboratories for Mass Spectrometry, University of Cincinnati, Cincinnati, OH 45221, USA and 3Centre de Ge´ ne´ tique Mole´ culaire, CNRS, Gif-sur-Yvette, F-91198, France Received August 29, 2013; Revised October 3, 2013; Accepted October 5, 2013 Downloaded from ABSTRACT Crick proposes how a single tRNA with G in the first position of the anticodon (also called the wobble base) Translation of the isoleucine codon AUA in most can read codons ending in U or C and how a tRNA prokaryotes requires a modified C (lysidine or with U (or a modified U) can read codons ending in A Ile http://nar.oxfordjournals.org/ agmatidine) at the wobble position of tRNA2 to or G (3–5). -
Discovery and Characterization of Trnaile Lysidine Synthetase (Tils)
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS Letters 584 (2010) 272–277 journal homepage: www.FEBSLetters.org Review Discovery and characterization of tRNAIle lysidine synthetase (TilS) Tsutomu Suzuki *, Kenjyo Miyauchi Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan article info abstract Article history: In the bacterial decoding system, the AUA codon is deciphered as isoleucine by tRNAIle bearing lysi- Received 12 November 2009 dine (L, 2-lysyl-cytidine) at the wobble position. Lysidine is an essential modification that deter- Revised 21 November 2009 mines both the codon and amino acid specificities of tRNAIle. We identified an enzyme named Accepted 24 November 2009 tRNAIle lysidine synthetase (TilS) that catalyzes lysidine formation by using lysine and ATP as sub- Available online 26 November 2009 strates. Biochemical studies revealed a molecular mechanism of lysidine formation that consists Edited by Manuel Santos of two consecutive reactions involving the adenylated tRNA intermediate. In addition, we deci- phered how Escherichia coli TilS specifically discriminates between tRNAIle and the structurally sim- ilar tRNAMet, which bears the same anticodon loop. Recent structural studies unveiled tRNA Keywords: tRNA recognition by TilS, and a molecular basis of lysidine formation at atomic resolution. Lysidine Ó 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. TilS AUA codon Wobble modification Anticodon 1. Lysidine plays a critical role in decoding the AUA codon as Ile tRNAIle bearing the CAU anticodon was switched to Met, and this tRNA translates the AUG codon as Met [4]. -
Expanding the Toolkit of Protein Engineering: Towards Multiple Simultaneous in Vivo Incorporation of Noncanonical Amino Acids
TECHNISCHE UNIVERSITÄT MÜNCHEN Max-Planck-Institut für Biochemie Expanding the Toolkit of Protein Engineering: Towards Multiple Simultaneous In Vivo Incorporation of Noncanonical Amino Acids Michael G. Hösl Vollständiger Abdruck der von der Fakultät für Chemie der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. Michael Groll Prüfer der Dissertation: 1. Univ.-Prof. Dr. Nediljko Budisa, Technische Universität Berlin 2. Univ.-Prof. Dr. Thomas Kiefhaber 3. Univ.-Prof. Dr. Johannes Buchner Die Dissertation wurde am 01.02.11 bei der Technischen Universität München eingereicht und durch die Fakultät für Chemie am 03.03.11 angenommen. To Teresa Ariadna García-Grajalva Lucas who influenced the idea of TAG → AGG switch just by the existence of her name Sleeping is giving in, no matter what the time is. Sleeping is giving in, so lift those heavy eyelids. People say that you'll die faster than without water. But we know it's just a lie, scare your son, scare your daughter. People say that your dreams are the only things that save ya. Come on baby in our dreams, we can live on misbehavior. The Arcade Fire Parts of this work were published as listed below: Hoesl, MG, Budisa, N. Expanding and engineering the genetic code in a single expression experiment. ChemBioChem 2011, 12, 552-555. Further publications: Hoesl, MG*, Staudt, H*, Dreuw, A, Budisa, N, Grininger, M, Oesterhelt, D, Wachtveitl, J. Manipulating the eletron transfer in Dodecin by isostructual noncanonical Trp analogs. 2011, [in preparation]. *authors contributed equally to this work Nehring, S*, Hoesl, MG*, Acevedo-Rocha, CG*, Royter, M, Wolschner, C, Wiltschi, B, Budisa, N, Antranikian, G. -
Broad and Adaptable RNA Structure Recognition by the Human Interferon-Induced Tetratricopeptide Repeat Protein IFIT5
Broad and adaptable RNA structure recognition by the human interferon-induced tetratricopeptide repeat protein IFIT5 George E. Katibaha, Yidan Qinb, David J. Sidoteb, Jun Yaob, Alan M. Lambowitzb,1, and Kathleen Collinsa,1 aDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720; and bInstitute for Cellular and Molecular Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712 Contributed by Alan M. Lambowitz, July 8, 2014 (sent for review April 29, 2014; reviewed by Sandra L. Wolin, Eric Phizicky, and Michael Gale, Jr.) Interferon (IFN) responses play key roles in cellular defense against copy numbers and combinations of four distinct IFIT proteins pathogens. Highly expressed IFN-induced proteins with tetratrico- (IFIT1, 2, 3, and 5) even within mammals, generated by paralog peptide repeats (IFITs) are proposed to function as RNA binding expansions and/or gene deletions, including the loss of IFIT5 in proteins, but the RNA binding and discrimination specificities of IFIT mice and rats (14). Human IFIT1, IFIT2, and IFIT3 coassemble proteins remain unclear. Here we show that human IFIT5 has in cells into poorly characterized multimeric complexes that ex- comparable affinity for RNAs with diverse phosphate-containing 5′- clude IFIT5 (15, 16). Recombinant IFIT family proteins range ends, excluding the higher eukaryotic mRNA cap. Systematic muta- from monomer to multimer, with crystal structures solved for genesis revealed that sequence substitutions in IFIT5 can alternatively a human IFIT2 homodimer (17), the human IFIT5 monomer expand or introduce bias in protein binding to RNAs with 5′ mono- (16, 18, 19), and an N-terminal fragment of human IFIT1 (18). -
Genome-Wide Investigation of Cellular Functions for Trna Nucleus
Genome-wide Investigation of Cellular Functions for tRNA Nucleus- Cytoplasm Trafficking in the Yeast Saccharomyces cerevisiae DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Hui-Yi Chu Graduate Program in Molecular, Cellular and Developmental Biology The Ohio State University 2012 Dissertation Committee: Anita K. Hopper, Advisor Stephen Osmani Kurt Fredrick Jane Jackman Copyright by Hui-Yi Chu 2012 Abstract In eukaryotic cells tRNAs are transcribed in the nucleus and exported to the cytoplasm for their essential role in protein synthesis. This export event was thought to be unidirectional. Surprisingly, several lines of evidence showed that mature cytoplasmic tRNAs shuttle between nucleus and cytoplasm and their distribution is nutrient-dependent. This newly discovered tRNA retrograde process is conserved from yeast to vertebrates. Although how exactly the tRNA nuclear-cytoplasmic trafficking is regulated is still under investigation, previous studies identified several transporters involved in tRNA subcellular dynamics. At least three members of the β-importin family function in tRNA nuclear-cytoplasmic intracellular movement: (1) Los1 functions in both the tRNA primary export and re-export processes; (2) Mtr10, directly or indirectly, is responsible for the constitutive retrograde import of cytoplasmic tRNA to the nucleus; (3) Msn5 functions solely in the re-export process. In this thesis I focus on the physiological role(s) of the tRNA nuclear retrograde pathway. One possibility is that nuclear accumulation of cytoplasmic tRNA serves to modulate translation of particular transcripts. To test this hypothesis, I compared expression profiles from non-translating mRNAs and polyribosome-bound translating mRNAs collected from msn5Δ and mtr10Δ mutants and wild-type cells, in fed or acute amino acid starvation conditions. -
FUNCTIONAL and MECHANISTIC CHARACTERIZATION of TWO TRNA MODIFYING ENZYMES LAURA CAROLE KEFFER-WILKES Master of Science, Universi
FUNCTIONAL AND MECHANISTIC CHARACTERIZATION OF TWO TRNA MODIFYING ENZYMES LAURA CAROLE KEFFER-WILKES Master of Science, University of Lethbridge, 2012 A Thesis Submitted to the School of Graduate Studies Of the University of Lethbridge In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY Department of Chemistry and Biochemistry University of Lethbridge LETHBRIDGE, ALBERTA, CANADA © Laura Keffer-Wilkes, 2016 FUNCTIONAL AND MECHANISTIC CHARACTERIZATION OF TWO TRNA MODIFYING ENZYMES LAURA CAROLE KEFFER-WILKES Date of Defence: June 28, 2016 Dr. Ute Wieden-Kothe Associate Professor Ph.D. Supervisor Dr. Tony Russell Assistant Professor Ph.D. Thesis Examination Committee Member Dr. Stacey Wetmore Professor Ph.D. Thesis Examination Committee Member Dr. Hans-Joachim Wieden Professor Ph.D. Thesis Examination Committee Member Dr. Eugene Mueller Professor Ph.D. External Examiner University of Louisville Louisville, Kentucky Dr. Elizabeth Schultz Associate Professor Ph.D. Internal External Examiner University of Lethbridge Dr. Michael Gerken Professor Ph.D. Chair, Thesis Examination Committee Abstract The formation of pseudouridine (Ѱ) and 5-methyluridine (m5U) in the T-arm of transfer RNAs (tRNAs) is near-universally conserved. These two modifications are formed in Escherichia coli by the pseudouridine synthase TruB and the S-adenosylmethionine- dependent methyltransferase TrmA, respectively. In this thesis, I investigate the function and mechanisms of these two tRNA modifying enzymes. First, in vitro and in vivo analysis of TruB reveals that this enzyme is acting as a tRNA chaperone which proves a long outstanding hypothesis. Secondly, characterization of ligand binding by TrmA shows that binding is cooperative and disruption of tRNA elbow region tertiary interactions by TrmA is essential for efficient tRNA binding and catalysis, leading to future analysis. -
Agmatidine, a Modified Cytidine in the Anticodon of Archaeal Trna , Base
Agmatidine, a modified cytidine in the anticodon of archaeal tRNAIle, base pairs with adenosine but not with guanosine Debabrata Mandala,1, Caroline Köhrera,1, Dan Sub, Susan P. Russellc, Kady Krivosc, Colette M. Castleberryc, Paul Blumd, Patrick A. Limbachc, Dieter Söllb, and Uttam L. RajBhandarya,2 aDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; bDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520; cDepartment of Chemistry, University of Cincinnati, Cincinnati, OH 45221; dGeorge Beadle Center for Genetics, University of Nebraska, Lincoln, NE 68588 Contributed by Dieter Söll, December 24, 2009 (sent for review December 2, 2009) Modification of the cytidine in the first anticodon position of the Eukaryotes, on the other hand, contain a tRNAIle with the anti- Ile Ile AUA decoding tRNA (tRNA2 ) of bacteria and archaea is essential codon IAU (I ¼ inosine), which can read all three isoleucine co- for this tRNA to read the isoleucine codon AUA and to differentiate dons using the wobble pairing rules of Crick. They also contain a between AUA and the methionine codon AUG. To identify the tRNAIle with the anticodon ΨAΨ, which is thought to read only modified cytidine in archaea, we have purified this tRNA species the isoleucine codon AUA but not the methionine codon AUG from Haloarcula marismortui, established its codon reading proper- (8). Given these two distinct mechanisms in bacteria and ties, used liquid chromatography–mass spectrometry (LC-MS) to eukaryotes, a question of much interest is how the archaeal map RNase A and T1 digestion products onto the tRNA, and used tRNAIle accomplishes the task of reading the AUA codon. -
Designing Minimal Genomes Using Whole-Cell Models
ARTICLE https://doi.org/10.1038/s41467-020-14545-0 OPEN Designing minimal genomes using whole-cell models ✉ Joshua Rees-Garbutt1,2,7, Oliver Chalkley1,3,4,7, Sophie Landon1,3, Oliver Purcell5, Lucia Marucci1,3,6,8 & ✉ Claire Grierson1,2,8 In the future, entire genomes tailored to specific functions and environments could be designed using computational tools. However, computational tools for genome design are 1234567890():,; currently scarce. Here we present algorithms that enable the use of design-simulate-test cycles for genome design, using genome minimisation as a proof-of-concept. Minimal gen- omes are ideal for this purpose as they have a simple functional assay whether the cell replicates or not. We used the first (and currently only published) whole-cell model for the bacterium Mycoplasma genitalium. Our computational design-simulate-test cycles discovered novel in silico minimal genomes which, if biologically correct, predict in vivo genomes smaller than JCVI-Syn3.0; a bacterium with, currently, the smallest genome that can be grown in pure culture. In the process, we identified 10 low essential genes and produced evidence for at least two Mycoplasma genitalium in silico minimal genomes. This work brings combined computational and laboratory genome engineering a step closer. 1 BrisSynBio, University of Bristol, Bristol BS8 1TQ, UK. 2 School of Biological Sciences, University of Bristol, Bristol Life Sciences Building, 24 Tyndall Avenue, Bristol BS8 1TQ, UK. 3 Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK. 4 Bristol Centre for Complexity Science, Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK.