Project

Back to overview

Metal Ions in Structure and Function of Regulatory RNAs

English title Metal Ions in Structure and Function of Regulatory RNAs
Applicant Sigel Roland K. O.
Number 165868
Funding scheme Project funding (Div. I-III)
Research institution Institut für Chemie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Inorganic Chemistry
Start/End 01.04.2016 - 31.03.2020
Approved amount 700'000.00
Show all

All Disciplines (2)

Discipline
Inorganic Chemistry
Biophysics

Keywords (7)

smFRET; NMR; Coordination Chemistry; Ribozymes; Riboswitches; Metal Ions; Regulatory RNA

Lay Summary (German)

Lead
Ribonucleinsäuren (RNA) sind essentiell für jedes Lebewesen. Regulatorische RNAs z.B. kontrollieren in einer lebenden Zelle Proteinexpression, deren Transport, oder auch den Lebenszyklus einer Zelle, indem sie die Transkription und/oder Translation entsprechender Gensequenzen regulieren. Die Faltung, Struktur, und Aktivität einer RNA hängt dabei von verschiedenen Faktoren ab, wie Metallionen und assoziierte Proteine. Riboschalter (riboswitch) können z.B. metallbasierte Metabolite wie Adenosylcobalamin (Coenzym B12) oder der Molybdenkofaktor (Moco) spezifisch binden und eine Änderung der dreidimensionalen Struktur als Mittel der Regulation einsetzen. Dieser Prozess ist äusserst empfindlich auf Änderungen in der Konzentration und Art der Metallionen, welche in einer Zelle vorhanden sind.
Lay summary

Das Ziel dieses Projektes ist es, die metallionenkontrollierte Struktur-Funktion-Beziehung von vier wichtigen RNAs aufzuschlüsseln und zu verstehen: (i) den bakteriellen Moco Riboschalter, (ii) einer oncogenen, in Tumorentstehung involvierte RNA G-Quadruplex, sowie zweier katalytisch aktiver RNAs, (iii) dem CPEB3 Ribozym, das einzige, das in Säugetieren bekannt ist und (iv) einem selbst-spleissenden Gruppe II Intron, welches als Vorläufer des grössten Teils des menschlichen Genoms gilt.

Durch eine einzigartige Kombination biochemischer und molekularbiologischer Methoden mit klassischer Koordinationschemie, sowie biomolekularer NMR- und Einzelmolekülspektroskopie können wir solche komplexen RNA Systeme detailliert in Bezug auf Struktur, Bindungs- und Faltungsgleichgewichte, sowie Dynamik untersuchen und verstehen. Angesiedelt in der klassischen Bioanorganischen Chemie, hat dieses Projekt auch einen grossen Einfluss auf die RNA Biochemie, die Strukturbiologie, sowie die Medizinische Chemie.

Direct link to Lay Summary Last update: 22.04.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts
Steffen Fabio D., Khier Mokrane, Kowerko Danny, Cunha Richard A., Börner Richard, Sigel Roland K. O. (2020), Metal ions and sugar puckering balance single-molecule kinetic heterogeneity in RNA and DNA tertiary contacts, in Nature Communications, 11(1), 104-104.
The Bioinorganic Periodic Table
Freisinger Eva, Sigel Roland K.O. (2019), The Bioinorganic Periodic Table, in CHIMIA International Journal for Chemistry, 73(3), 185-193.
Specific phosphorothioate substitution within domain 6 of a group II intron ribozyme leads to changes in local structure and metal ion binding
Erat Michèle C., Besic Emina, Oberhuber Michael, Johannsen Silke, Sigel Roland K. O. (2018), Specific phosphorothioate substitution within domain 6 of a group II intron ribozyme leads to changes in local structure and metal ion binding, in JBIC Journal of Biological Inorganic Chemistry, 23(1), 167-177.
The Role of Lead(II) in Nucleic Acids
Palou-Mir Joana, Barceló-Oliver Miquel, Sigel Roland K. O. (2017), The Role of Lead(II) in Nucleic Acids, in Sigel Roland K.O., Sigel Astrid, Sigel Helmut (ed.), De Gruyter, Berlin, Boston, 403-434.
G-quadruplex DNA targeted metal complexes acting as potential anticancer drugs
Cao Qian, Li Yi, Freisinger Eva, Qin Peter Z., Sigel Roland K. O., Mao Zong-Wan (2017), G-quadruplex DNA targeted metal complexes acting as potential anticancer drugs, in Inorganic Chemistry Frontiers, 4(1), 10-32.
Influence of pH and Mg( ii ) on the catalytic core domain 5 of a bacterial group II intron
Pechlaner M., Dominguez-Martin A., Sigel R. K. O. (2017), Influence of pH and Mg( ii ) on the catalytic core domain 5 of a bacterial group II intron, in Dalton Transactions, 46(12), 3989-3995.
Distinct differences in metal ion specificity of RNA and DNA G-quadruplexes
Guiset Miserachs Helena, Donghi Daniela, Börner Richard, Johannsen Silke, Sigel Roland K. O. (2016), Distinct differences in metal ion specificity of RNA and DNA G-quadruplexes, in JBIC Journal of Biological Inorganic Chemistry, 21(8), 975-986.
Metal ion induced heterogeneity in RNA folding studied by smFRET
Börner Richard, Kowerko Danny, Miserachs Helena Guiset, Schaffer Michelle F., Sigel Roland K.O. (2016), Metal ion induced heterogeneity in RNA folding studied by smFRET, in Coordination Chemistry Reviews, 327-328, 123-142.
The X-ray Structures of Six Octameric RNA Duplexes in the Presence of Different Di- and Trivalent Cations
Schaffer Michelle, Peng Guanya, Spingler Bernhard, Schnabl Joachim, Wang Meitian, Olieric Vincent, Sigel Roland (2016), The X-ray Structures of Six Octameric RNA Duplexes in the Presence of Different Di- and Trivalent Cations, in International Journal of Molecular Sciences, 17(7), 988-988.

Collaboration

Group / person Country
Types of collaboration
CERM, Florence Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
PD. Dr. Eva Freisinger Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Dr. Meitian Wan & Dr. Vincent Olieric, PSI Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Dr. Helena Kovacs, Bruker Biospin, Fällanden (ZH) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Dr. Ramon Vilar, Imperial College London Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof. Dr. Zongwan Mao, Sun Yat Sen University, Guangzhou China (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof. Dr. Günter Schwarz Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
SCS Fall Meeting 2019 Poster The HDV-Like Family: Crystal Structure Of The CPEB3 Ribozyme 06.09.2019 Zürich, Switzerland Przytula-Mally Anna Ilaria;
SCS Fall Meeting 2019 Poster Searching For The Metabolite That Triggers The Moco Riboswitch 06.09.2019 Zürich, Switzerland Amadei Fabio;
SCS Fall Meeting 2019 Poster Determination Of The NMR Solution Structure Of The CPEB3 Ribozyme 06.09.2019 Zürich, Switzerland Markova Irina;
International Conference on Bioinorganic Chemistry (ICBIC-19) Talk given at a conference Hunting For The Identity Of The Missing Metabolite Of The Moco Riboswitch In The Moco Biosynthetic Pathwa 11.08.2019 Interlaken, Switzerland Amadei Fabio;
International Conference on Bioinorganic Chemistry (ICBIC-19) Poster Photophysical Study on the Interaction between RNA G-quadruplex and Pt(II) Complexes 11.08.2019 Interlaken, Switzerland Wang Zenghui;
International Conference on Bioinorganic Chemistry (ICBIC-19) Poster Determination Of The NMR Solution Structure Of The CPEB3 Ribozyme 11.08.2019 Interlaken, Switzerland Markova Irina;
International Conference on Bioinorganic Chemistry (ICBIC-19) Poster Solving The 1st Structure From The HDV-Like Ribozyme Family: The CPEB3 Ribozyme 11.08.2019 Interlaken, Switzerland Przytula-Mally Anna Ilaria;
24th Annual Meeting of the RNA Society Poster The HDV-Like Family: Crystal Structure Of The CPEB3 Ribozyme 11.06.2019 Krakau, Poland Amadei Fabio;
24th Annual Meeting of the RNA Society Poster Crystallization Of Human And Chimp CPEB3 Ribozymes 11.06.2019 Krakau, Poland Przytula-Mally Anna Ilaria;
MIIBSXS Summer School 2019 Poster Solving The 1st Structure From The HDV-Like Ribozyme Family: The CPEB3 Ribozyme 12.05.2019 Oeiras, Portugal Przytula-Mally Anna Ilaria;
9th Asian Biological Inorganic Chemistry Conference (AsBIC-9) Talk given at a conference RNA Self-Splicing – A Biophysical-Bioinorganic View 09.12.2018 Singapur, Singapore Sigel Roland K. O.;
Seminar at the University of Hong-Kong Individual talk RNA Folding In Bulk And On The Single Molecule Level 19.11.2018 Hongkong, Hongkong Sigel Roland K. O.;
Knut and Alice Wallenberg Foundation Visit Individual talk Tweaking Structure And Function - Metal Ions In The Core Of Single Ribozymes And Riboswitches 28.09.2018 Zürich, Switzerland Sigel Roland K. O.;
SCS Fall Meeting 2018 Poster Probing The NMR Solutuion Structure Of The CPEB3 Ribozyme 07.09.2018 Lausanne, Switzerland Markova Irina;
SCS Fall Meeting 2018 Poster Towards Trapping The Mammalian CPEB3 Ribozyme Into A Crystal 07.09.2018 Lausanne, Switzerland Przytula-Mally Anna Ilaria;
XIV International Symposium on Inorganic Biochemistry Talk given at a conference An Multifaceted View On A Metal Iondirected RNA-RNA Interaction 05.09.2018 Wroclaw, Poland Sigel Roland K. O.;
14th European Biological Inorganic Chemistry Conference (EuroBIC 14 ) Talk given at a conference RNA Folding And Self-Splicing – A Biophysical-Bioinorganic View 26.08.2018 Birmingham, Great Britain and Northern Ireland Wang Zenghui;
XXVIII International Conference on Magnetic Resonance in Biological Systems (ICMRBS) Poster Probing the NMR Solutuion Structure of the CPEB3 Ribozyme 19.08.2018 Dublin, Ireland Markova Irina;
XXVIII International Conference on Magnetic Resonance in Biological Systems (ICMRBS) Talk given at a conference Probing The CPEB3 Structure By NMR 19.08.2018 Dublin, Ireland Markova Irina;
XI Molybdenum & Tungsten Enzyme Conference 2019 Poster Searching For The Metabolite That Triggers The Moco Riboswitch 07.07.2018 Potsdam, Germany Amadei Fabio;
Workshop Chemistry for the Future Individual talk Strategies To Crystallize The 1st Human Ribozyme: The CPEB3 Ribozyme And Its Mutants 04.07.2018 Pisa, Italy Sigel Roland K. O.;
23rd Annual Meeting of the RNA Society Poster Probing The CPEB3 RNA Structure By NMR 29.05.2018 Berkeley, United States of America Przytula-Mally Anna Ilaria;
Abstracts of the Swiss RNA Workshop 2018 Poster Unwinding The Double Pseudoknot Of The HDV-Like Ribozyme Family 02.02.2018 Bern, Switzerland Przytula-Mally Anna Ilaria;
Abstracts of the Swiss RNA Workshop 2018 Poster A Promising Riboswitch Candidate Involved In The Molybdenum Cofactor Metabolism 02.02.2018 Bern, Switzerland Amadei Fabio;
Gordon Research Conference on Metals in Biology Talk given at a conference Tweaking Structure and Function - Metal Ions in the Core of Single Ribozymes and Riboswitches 21.01.2018 Ventura, United States of America Sigel Roland K. O.;
Lecture at the University of California at Irvine Individual talk RNA Folding in Bulk and on the Single Molecule Level 19.01.2018 Irvine,, United States of America Sigel Roland K. O.;
The 2nd International Symposium on Biofunctional Chemistry (ISBC 2017) Talk given at a conference Changing Structure And Folding Pathway Of Rnas By Metal Ions And Their Complexes 14.12.2017 Kyoto, Japan Sigel Roland K. O.;
The First International Symposium on Chemistry for Multimolecular Crowding Biosystems (CMCB 2017) Talk given at a conference RNA Folding In Bulk And On The Single Molecule Level 12.12.2017 Kobe, Japan Sigel Roland K. O.;
Saminar at the Max Planck Institute for Biophysics Individual talk Changing Structure And Folding Pathway Of Rnas By Metal Ions And Their Complexes 24.11.2017 Frankfurt a. M., Germany Sigel Roland K. O.;
Seminat at the Lorentz Center Individual talk Photophysical Insight On The Interaction Between An RNA G-Quadruplex And Fluorescent Platinum(II) Complexes 30.10.2017 Leiden, Netherlands Sigel Roland K. O.;
SCS Fall Meeting 2018 Poster Photophysical Investigation On The Interaction Between Pt(II) Complexes And An RNA G-Quadruplex 07.09.2017 Lausanne, Switzerland Wang Zenghui;
14th European Biological Inorganic Chemistry Conference (EuroBIC 14 ) Talk given at a conference Metal Ions At The Heart Of RNAs 26.08.2017 Birmingham, Great Britain and Northern Ireland Sigel Roland K. O.;
SCS Fall Meeting 2017 Poster Dynamic Insight Into The Interaction Between Two Fluorescent Platinum(II) Complexes And A BCL-2 RNA G-Quadruplex 21.08.2017 Bern, Switzerland Amadei Fabio;
SCS Fall Meeting 2017 Poster The Moco Riboswitch: The Missing Metabolite 21.08.2017 Bern, Switzerland Markova Irina;
SCS Fall Meeting 2017 Poster Labeling, Mutations And Truncated Constructs: Approach To Solving The Structure Of The CPEB3 Ribozyme Through NMR Spectroscopy 21.08.2017 Bern, Switzerland Wang Zenghui;
International Conference on Biological Inorganic Chemistry (ICBIC18) Talk given at a conference The Moco Riboswitch: Structural And Functional Studies 31.07.2017 Florianopolis, Brazil Sigel Roland K. O.;
International Conference on Biological Inorganic Chemistry (ICBIC18) Talk given at a conference Catalytic Rnas In Humans - The Mammalian CPEB3 Ribozyme 31.07.2017 Florianopolis, Brazil Wang Zenghui;
Molybdenum and Tungsten Enzymes Conference (MoTEC) Poster RNA G-Quadruplex Structures And Binding To Pt(II) Coplexes 18.06.2017 Santa Fee, United States of America Amadei Fabio;
14th International Symposium on Applied Bioinorganic Chemistry (ISABC14) Talk given at a conference A Photophysical Study On The Interaction Between Fluorescent Platinum(II) Complexes And A BCL-2 RNA G-Quadruplex 07.06.2017 Toulouse, France Sigel Roland K. O.;
6th International Meeting on Quadruplex Nucleic Acids: G4thering Poster Folding And Splicing Of Group II Intron Ribozymes At The Single Molecule Level 31.05.2017 Prag, Czech Republic Sigel Roland K. O.;
6th International Meeting on Quadruplex Nucleic Acids: G4thering Poster Isolation And Characterization Of Various Equilibrium Structures Of The BCL2 RNA G-4plex And Their Interaction With Metal Complexes 31.05.2017 Prag, Czech Republic Wang Zenghui;
22nd Annual Meeting of the RNA Society Talk given at a conference NMR Spectroscopy 30.05.2017 Prag, Czech Republic Sigel Roland K. O.;
22nd Annual Meeting of the RNA Society Poster Facing The Challenge Of Solving The Solution Structure Of The Cytoplasmic Element Binding Protein 3 Ribozyme By NMR Spectroscopy 30.05.2017 Prag, Czech Republic Kenneth Adea;
23rd Annual Meeting of the RNA Society Poster A Promising Riboswitch Candidate Involved In The Molybdenum Cofactor Metabolism 29.05.2017 Berkeley, United States of America Amadei Fabio;
FEBS Summer School Metals in Biological Systems Poster Investigation Of A New Promising Riboswitch Candidate By Footprinting Assays 21.05.2017 Louvain-la-Neuve, Belgium Amadei Fabio;
FEBS Summer School Metals in Biological Systems Talk given at a conference Bioinorganic Chemistry Of RNA: How Metal Ions Influence The Folding, Structure And Mechanism Of Large RNA 21.05.2017 Louvain-la-Neuve, Belgium Sigel Roland K. O.;
Swiss RNA Workshop Poster Tackling The Challenge Of Solving The Solution Structure Of The CPEB3 Ribozyme Through NMR Spectroscopy Using Several Strategies 27.01.2017 Bern, Switzerland Kenneth Adea;
Swiss RNA Workshop Poster The Moco Riboswitch From E. Coli 27.01.2017 Bern, Switzerland Amadei Fabio;
9th Asian Biological Inorganic Chemistry Conference (AsBIC-9) Talk given at a conference Switching and Twitching of Regulatory RNAs by Metal Ions and Their Complexes 04.12.2016 Auckland, New Zealand Sigel Roland K. O.;
11th Dorothy Crowfoot Hodgkin Symposium Poster Solving The Solution Structure Of A Mammalian Ribozyme Through Nuclear Magnetic Resonance Spectroscopy 03.10.2016 Zürich, Switzerland Kenneth Adea;
11th Dorothy Crowfoot Hodgkin Symposium Poster Investigations On The Interaction Between Platinum Metal Complex And RNA G-Quadruplex 03.10.2016 Zürich, Switzerland Wang Zenghui;
SCS Fall Meeting 2016 Poster The Moco riboswitch from E.coli 15.09.2016 Zürich, Switzerland Amadei Fabio;
SCS Fall Meeting 2016 Poster Strategies To Solve The Solution Structure Of The CPEB3 Ribozyme Through NMR Spectroscop 15.09.2016 Zürich, Switzerland Kenneth Adea;
3th European Biological Inorganic Chemistry Conference (EuroBIC-13) Poster Interaction Between The Molybdenum Cofactor (Moco) And The Moco Riboswitch From E. Coli 28.08.2016 Budapest, Hungary Amadei Fabio;
3th European Biological Inorganic Chemistry Conference (EuroBIC-13) Poster Investigations On The Interaction Between Platinum Metal Complex And RNA G-Quadruplex 28.08.2016 Budapest, Hungary Wang Zenghui;
3th European Biological Inorganic Chemistry Conference (EuroBIC-13) Talk given at a conference Metal Ions And Protons Shaping The Structure And Function Of A Mammalian Ribozyme 28.08.2016 Budapest, Hungary Sigel Roland K. O.;
SCS Fall Meeting 2017 Poster Probing The CPEB3 Structure By NMR 21.08.2016 Bern, Switzerland Kenneth Adea;
10h Class for MSc and PhD students, University of the Balearic Islands Individual talk Bioinorganic Chemistry – Nucleic Acids And Metal Ions 06.06.2016 Palma de Mallorca, Spain Sigel Roland K. O.;
3rd Symposium on Functional Metal Complexes that Bind to Biomolecules, COST Action CM1105 Talk given at a conference Metal Ion Assisted Folding Of Two RNA Structures: G-Quadruplexes And A Mammalian Ribozyme 28.04.2016 Palma de Mallorca, Spain Sigel Roland K. O.;


Self-organised

Title Date Place

Awards

Title Year
Best Oral Presentation Award at the ICBIC 18 2018
EuroBIC14 Travel Award 2018
ICBIC 2018 Travel Grant 2018
LS2 Travel Grant 2018
RNA Society Travel Grant 2018
Poster Prize at the 10th Molybdenum and Tungsten Enzyme Conference 2017
FEBS Travel Grant 2017
ISBC 2017 Travel Grant 2017

Associated projects

Number Title Start Funding scheme
143750 Metal Ion-Guided Assembly and Structures of the Catalytic Core of Ribozymes 01.10.2012 Project funding (Div. I-III)
192153 Principles of Metal-Ion-Assisted Folding and Structure of Functional RNAs 01.04.2020 Project funding (Div. I-III)

Abstract

RNAs play crucial roles in cellular metabolism. Regulatory RNAs thereby control uncountable processes in all kingdoms of life, e.g. protein expression and transport or the cell cycle, mostly on the transcriptional or the translational level. Folding, structure, and activity of any RNA are guided tightly by metal ions, in some instances also in combination with proteins. In the case of some riboswitches, metal-based metabolites, e.g., adenosyl cobalamin (AdoCbl) or molybdenum cofactor (Moco), specifically bind and switch the RNA structure. Switching, folding, structure, and catalysis of RNAs are extremely sensitive to changes in concentration and nature of the metal ion(s) (complexes). Recognition of the metal ions or its complex is thereby solely driven by coordination chemical principles. The goal of this project is to understand the structure-function relationship under control of metal ions of four key RNAs: (i) the bacterial Moco riboswitch, (ii) an oncogenic RNA G-quadruplex, (iii) the mammalian CPEB3 ribozyme, and (iv) a self-splicing group II intron. The combination of biochemical tools, coordination chemistry, biomolecular NMR spectroscopy, and single molecule (sm)FRET provides a unique and exceptional possibility to understand such complex RNAs in detail with respect to structure, thermodynamic and kinetic. This project is located in the classical field of Biological Inorganic Chemistry, but also has a great impact on RNA Biochemistry, Structural Biology, and Medicinal Chemistry.
-