Characterization of UVA-Induced Alterations to Transfer RNA Sequences
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Investigation of Overhauser Effects Between Pseudouridine and Water Protons in RNA Helices
Investigation of Overhauser effects between pseudouridine and water protons in RNA helices Meredith I. Newby* and Nancy L. Greenbaum*†‡ *Department of Chemistry and Biochemistry and †Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306-4390 Communicated by Michael Kasha, Florida State University, Tallahassee, FL, August 8, 2002 (received for review July 2, 2002) The inherent chemical properties of RNA molecules are expanded by posttranscriptional modification of specific nucleotides. Pseudouridine (), the most abundant of the modified bases, features an additional imino group, NH1, as compared with uri- dine. When forms a Watson–Crick base pair with adenine in an RNA helix, NH1 is positioned within the major groove. The pres- ence of often increases thermal stability of the helix or loop in which it is found [Hall, K. B. & McLaughlin, L. (1992) Nucleic Acids Res. 20, 1883–1889]. X-ray crystal structures of transfer RNAs [e.g., Arnez, J. & Steitz, T. (1994) Biochemistry 33, 7560–7567] have depicted water molecules bridging NH1 groups and nearby phos- phate oxygen atoms, but direct evidence for this interaction in solution has not been acquired. Toward this end, we have used a rotating-frame Overhauser effect spectroscopy-type NMR pulse sequence with a CLEAN chemical-exchange spectroscopy spin-lock pulse train [Hwang, T.-L., Mori, S., Shaka, A. J. & van Zijl, P. C. M. Fig. 1. Schematic structures of U and bases. R, ribose. The base is a uracil (1997) J. Am. Chem. Soc. 119, 6203–6204] to test for NH1–water rotated about the 3–6 ring axis, so that is has a COC base–sugar linkage and cross-relaxation effects within two RNA helices: (i) a complemen- an additional protonated ring nitrogen. -
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). -
The Human Ortholog of Archaeal Pus10 Produces Pseudouridine 54 in Select Trnas Where Its Recognition Sequence Contains a Modified Residue
Downloaded from rnajournal.cshlp.org on October 7, 2021 - Published by Cold Spring Harbor Laboratory Press The human ortholog of archaeal Pus10 produces pseudouridine 54 in select tRNAs where its recognition sequence contains a modified residue MANISHA DEOGHARIA,1 SHAONI MUKHOPADHYAY, ARCHI JOARDAR,2 and RAMESH GUPTA Department of Biochemistry and Molecular Biology, Southern Illinois University, Carbondale, Illinois 62901-4413, USA ABSTRACT The nearly conserved U54 of tRNA is mostly converted to a version of ribothymidine (T) in Bacteria and eukaryotes and to a version of pseudouridine (Ψ) in Archaea. Conserved U55 is nearly always modified to Ψ55 in all organisms. Orthologs of TrmA and TruB that produce T54 and Ψ55, respectively, in Bacteria and eukaryotes are absent in Archaea. Pus10 produces both Ψ54 and Ψ55 in Archaea. Pus10 orthologs are found in nearly all sequenced archaeal and most eukaryal genomes, but not in yeast and bacteria. This coincides with the presence of Ψ54 in most archaeal tRNAs and some animal tRNAs, but its absence from yeast and bacteria. Moreover, Ψ54 is found in several tRNAs that function as primers for retroviral DNA syn- thesis. Previously, no eukaryotic tRNA Ψ54 synthase had been identified. We show here that human Pus10 can produce Ψ54 in select tRNAs, including tRNALys3, the primer for HIV reverse transcriptase. This synthase activity of Pus10 is restrict- ed to the cytoplasm and is distinct from nuclear Pus10, which is known to be involved in apoptosis. The sequence GUUCAm1AAUC (m1A is 1-methyladenosine) at position 53–61 of tRNA along with a stable acceptor stem results in max- imum Ψ54 synthase activity. -
Pseudouridine Synthases Modify Human Pre-Mrna Co-Transcriptionally and Affect Splicing
bioRxiv preprint doi: https://doi.org/10.1101/2020.08.29.273565; this version posted August 31, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect splicing Authors: Nicole M. Martinez1, Amanda Su1, Julia K. Nussbacher2,3,4, Margaret C. Burns2,3,4, Cassandra Schaening5, Shashank Sathe2,3,4, Gene W. Yeo2,3,4* and Wendy V. Gilbert1* Authors and order TBD with final revision. Affiliations: 1Yale School of Medicine, Department of Molecular Biophysics & Biochemistry, New Haven, CT 06520, USA. 2Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA. 3Stem Cell Program, University of California, San Diego, La Jolla, CA 92037, USA. 4Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92037, USA. 5Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. *Correspondence to: [email protected], [email protected] Abstract: Eukaryotic messenger RNAs are extensively decorated with modified nucleotides and the resulting epitranscriptome plays important regulatory roles in cells 1. Pseudouridine (Ψ) is a modified nucleotide that is prevalent in human mRNAs and can be dynamically regulated 2–5. However, it is unclear when in their life cycle RNAs become pseudouridylated and what the endogenous functions of mRNA pseudouridylation are. To determine if pseudouridine is added co-transcriptionally, we conducted pseudouridine profiling 2 on chromatin-associated RNA to reveal thousands of intronic pseudouridines in nascent pre-mRNA at locations that are significantly associated with alternatively spliced exons, enriched near splice sites, and overlap hundreds of binding sites for regulatory RNA binding proteins. -
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. -
A Dissertation Entitled Ribonucleic Acids in Disease Etiology and Drug Discovery by Immaculate Sappy Submitted to the Graduate F
A Dissertation entitled Ribonucleic Acids in Disease Etiology and Drug Discovery by Immaculate Sappy Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Medicinal Chemistry ________________________________________ Amanda C. Bryant-Friedrich, Ph.D., Committee Chair ________________________________________ Zahoor A Shah, Ph.D., Committee Member ________________________________________ Steven M Peseckis, Ph.D., Committee Member ________________________________________ Caren Steinmiller, Ph.D., Committee Member ________________________________________ Amanda Bryant-Friedrich, PhD, Dean College of Graduate Studies The University of Toledo December 2019 Copyright 2019, Immaculate Sappy This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of Ribonucleic Acids in Disease Etiology and Drug Discovery by Immaculate Sappy Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Medicinal Chemistry The University of Toledo December 2019 Pseudouridine (Ψ), the 5-ribosyl isomer of uridine (U) is the most abundant nucleic acid modification found in all domains of life and all types of RNA. Studies have shown that, urinary levels of pseudouridine are higher in Alzheimer’s Disease (AD) patients and that RNA oxidation is a major component in the pathogenesis of Alzheimer’s Disease (AD) and other neurodegenerative disorders. Therefore, there is a potential correlation between higher urinary levels of pseudouridine in AD patients and oxidative stress. Hence, subjecting pseudouridine to oxidative conditions may provide some key information about the role of this nucleoside in RNA related processes and its role in disease etiology. Besides neurodegenerative disorders, antibiotic resistance is an additional threat to human health. -
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. -
Increased Excretion of Modified Adenine Nucleosides by Children with Adenosine Dearninase Deficiency
Pediatr. Res. 16: 362-369 (1982) Increased Excretion of Modified Adenine Nucleosides by Children with Adenosine Dearninase Deficiency ROCHELLE HIRSCHHORN,'"~ HOWARD RATECH, ARYE RUBINSTEIN, PHOTINI PAPAGEORGIOU, HERNANT KESARWALA, ERWIN GELFAND, AND VIVIEN ROEGNER-MANISCALCO Departments of Medicine and Pathology, New York University School of Medicine, New York, New York [R.H., H.R., and V.R.-M.];Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York [A.R.]; Department of Pediatrics, Rutgers University Medical ~chool,Piscataway, New Jersey [P.P., and H.K.]; and Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada [E. G.] Summary tially in, and prevents proliferation of, irnmunocompetent cells, primarily of the T cell class (2, 5, 6, 23, 38, 49, 54). There is also We have identified seven adenine nucleosides in urines of un- in vivo and/or in vitro evidence for alternative mechanisms of treated adenosine deaminase (ADA) deficient patients, four of toxicity, which would operate via depletion of pyrimidine pools, which (adenosine, 2'-deoxyadenosine, 1-methyladenosine and N6- depletion of phosphoribosyl pyrophosphate and increases in cyclic methyladenosine) have been previously identified in urines of AMP or S-adenosyl homocysteine (16, 21, 24, 40, 46, 55). All of normals and/or ADA deficient patients. We confirm that ADA these mechanisms are dependent on accumulation of the substrates deficient patients excrete markedly increased amounts of 2'-deox- of ADA, adenosine and 2'-deoxyadenosine. yadenosine (582 k 363 versus normal of < 0.1 nmoles/mg creati- In addition to adenosine and 2'-deoxyadenosine, several other nine) and increased amounts of adenosine (29.4 & 5.7 versus modified adenine nucleosides occur naturally (17, 19) and are normal of 4.12 & 1.0 nmoles/mg creatinine). -
N4-Acetylcytidine and 5-Formylcytidine Are Present in Saccharomyces Cerevisiae Mrnas
bioRxiv preprint doi: https://doi.org/10.1101/327585; this version posted May 21, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. N4-acetylcytidine and 5-formylcytidine are present in Saccharomyces cerevisiae mRNAs Mehmet Tardu1, Qishan Lin2, and Kristin S. Koutmou1* 1University of Michigan, Department of Chemistry, 930 N University, Ann Arbor, MI 48109, (734) 764-5650, [email protected], 2Mass Spectrometry Consortium for Epitranscriptomics, University at Albany, 1400 Washington Ave, Albany, NY 12222. Abstract Chemical modifications of RNAs have long been appreciated as key modulators of non-coding RNA structure and function. There is an emerging realization that chemical modification of protein-coding mRNAs also plays critical roles in the cell. Nonetheless, of the over 100 known RNA modifications found in biology only a handful have been identified in mRNAs. Here we use an ultra-high performance liquid chromatography- tandem mass spectrometry (UHPLC-MS/MS) method to identify and quantify modifications present in mRNAs of yeast cells. We detect the presence of four modified nucleosides in mRNAs at relatively high abundances: N7-methylguanosine, N6- methyladenosine, N4-acetylcytidine and 5-formylcytidine. Additionally, we investigate how the levels of mRNA modifications change in response to cellular stress. We find that the concentrations of nine mRNA modifications including N6-methyladenosine and N4- acetylcytidine change in response to heat stress, glucose starvation and/or oxidative stress. Our findings suggest that mRNA modification may provide a potential mechanism for cells to rapidly respond to environmental stressors. -
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]. -
Modified Nucleosides, Nucleotides, and Nucleic
(19) TZZ ¥Z__T (11) EP 2 763 701 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 48/00 (2006.01) C07H 21/02 (2006.01) 19.12.2018 Bulletin 2018/51 C07H 21/04 (2006.01) (21) Application number: 12838676.0 (86) International application number: PCT/US2012/058519 (22) Date of filing: 03.10.2012 (87) International publication number: WO 2013/052523 (11.04.2013 Gazette 2013/15) (54) MODIFIED NUCLEOSIDES, NUCLEOTIDES, AND NUCLEIC ACIDS, AND USES THEREOF MODIFIZIERTE NUKLEOSIDE, NUKLEOTIDE UND NUKLEINSÄUREN UND VERWENDUNGEN DAVON NUCLÉOSIDES, NUCLÉOTIDES ET ACIDES NUCLÉIQUES MODIFIÉS, ET LEURS UTILISATIONS (84) Designated Contracting States: (74) Representative: Hoffmann Eitle AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Patent- und Rechtsanwälte PartmbB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Arabellastraße 30 PL PT RO RS SE SI SK SM TR 81925 München (DE) Designated Extension States: BA ME (56) References cited: WO-A2-2011/012316 US-A1- 2010 047 261 (30) Priority: 03.10.2011 US 201161542533 P US-A1- 2011 143 397 US-A1- 2012 251 618 (43) Date of publication of application: • KARIKÓ KATALIN ET AL: "Incorporation of 13.08.2014 Bulletin 2014/33 pseudouridine into mRNA yields superior nonimmunogenic vector with increased (73) Proprietor: Moderna Therapeutics, Inc. translational capacity and biological stability", Cambridge, Massachusetts 02141 (US) MOLECULAR THERAPY, NATURE PUBLISHING GROUP, GB, vol. 16, no. 11, 1 November 2008 (72) Inventors: (2008-11-01), pages 1833-1840, XP002598556, • DE FOUGEROLLES, Antonin ISSN: 1525-0024, DOI: 10.1038/MT.2008.200 Brookline, MA 02446 (US) [retrieved on 2008-09-16] •ROY,Atanu • LUIGI WARREN ET AL: "Highly efficient Stoneham, MA 02180 (US) reprogramming to pluripotency and directed • SCHRUM, Jason P.