The Dynamics of Subunit Rotation in a Eukaryotic Ribosome
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Crystal Structure of the Eukaryotic 60S Ribosomal Subunit in Complex with Initiation Factor 6
Research Collection Doctoral Thesis Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6 Author(s): Voigts-Hoffmann, Felix Publication Date: 2012 Permanent Link: https://doi.org/10.3929/ethz-a-007303759 Rights / License: In Copyright - Non-Commercial Use Permitted This page was generated automatically upon download from the ETH Zurich Research Collection. For more information please consult the Terms of use. ETH Library ETH Zurich Dissertation No. 20189 Crystal Structure of the Eukaryotic 60S Ribosomal Subunit in Complex with Initiation Factor 6 A dissertation submitted to ETH ZÜRICH for the degree of Doctor of Sciences (Dr. sc. ETH Zurich) presented by Felix Voigts-Hoffmann MSc Molecular Biotechnology, Universität Heidelberg born April 11, 1981 citizen of Göttingen, Germany accepted on recommendation of Prof. Dr. Nenad Ban (Examiner) Prof. Dr. Raimund Dutzler (Co-examiner) Prof. Dr. Rudolf Glockshuber (Co-examiner) 2012 blank page ii Summary Ribosomes are large complexes of several ribosomal RNAs and dozens of proteins, which catalyze the synthesis of proteins according to the sequence encoded in messenger RNA. Over the last decade, prokaryotic ribosome structures have provided the basis for a mechanistic understanding of protein synthesis. While the core functional centers are conserved in all kingdoms, eukaryotic ribosomes are much larger than archaeal or bacterial ribosomes. Eukaryotic ribosomal rRNA and proteins contain extensions or insertions to the prokaryotic core, and many eukaryotic proteins do not have prokaryotic counterparts. Furthermore, translation regulation and ribosome biogenesis is much more complex in eukaryotes, and defects in components of the translation machinery are associated with human diseases and cancer. -
Micrornas Mediated Regulation of the Ribosomal Proteins and Its Consequences on the Global Translation of Proteins
cells Review microRNAs Mediated Regulation of the Ribosomal Proteins and Its Consequences on the Global Translation of Proteins Abu Musa Md Talimur Reza 1,2 and Yu-Guo Yuan 1,3,* 1 Jiangsu Co-Innovation Center of Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; [email protected] 2 Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawi´nskiego5a, 02-106 Warsaw, Poland 3 Jiangsu Key Laboratory of Zoonosis/Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China * Correspondence: [email protected]; Tel.: +86-514-8797-9228 Abstract: Ribosomal proteins (RPs) are mostly derived from the energy-consuming enzyme families such as ATP-dependent RNA helicases, AAA-ATPases, GTPases and kinases, and are important structural components of the ribosome, which is a supramolecular ribonucleoprotein complex, composed of Ribosomal RNA (rRNA) and RPs, coordinates the translation and synthesis of proteins with the help of transfer RNA (tRNA) and other factors. Not all RPs are indispensable; in other words, the ribosome could be functional and could continue the translation of proteins instead of lacking in some of the RPs. However, the lack of many RPs could result in severe defects in the biogenesis of ribosomes, which could directly influence the overall translation processes and global expression of the proteins leading to the emergence of different diseases including cancer. While microRNAs (miRNAs) are small non-coding RNAs and one of the potent regulators of the post-transcriptional 0 gene expression, miRNAs regulate gene expression by targeting the 3 untranslated region and/or coding region of the messenger RNAs (mRNAs), and by interacting with the 50 untranslated region, Citation: Reza, A.M.M.T.; Yuan, Y.-G. -
History of the Ribosome and the Origin of Translation
History of the ribosome and the origin of translation Anton S. Petrova,1, Burak Gulena, Ashlyn M. Norrisa, Nicholas A. Kovacsa, Chad R. Berniera, Kathryn A. Laniera, George E. Foxb, Stephen C. Harveyc, Roger M. Wartellc, Nicholas V. Huda, and Loren Dean Williamsa,1 aSchool of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332; bDepartment of Biology and Biochemistry, University of Houston, Houston, TX, 77204; and cSchool of Biology, Georgia Institute of Technology, Atlanta, GA 30332 Edited by David M. Hillis, The University of Texas at Austin, Austin, TX, and approved November 6, 2015 (received for review May 18, 2015) We present a molecular-level model for the origin and evolution of building up of the functional centers, proceeds to the establishment the translation system, using a 3D comparative method. In this model, of the common core, and continues to the development of large the ribosome evolved by accretion, recursively adding expansion metazoan rRNAs. segments, iteratively growing, subsuming, and freezing the rRNA. Incremental evolution of function is mapped out by stepwise Functions of expansion segments in the ancestral ribosome are accretion of rRNA. In the extant ribosome, specific segments of assigned by correspondence with their functions in the extant rRNA perform specific functions including peptidyl transfer, ribosome. The model explains the evolution of the large ribosomal subunit association, decoding, and energy-driven translocation subunit, the small ribosomal subunit, tRNA, and mRNA. Prokaryotic (11). The model assumes that the correlations of rRNA segments ribosomes evolved in six phases, sequentially acquiring capabilities with their functions have been reasonably maintained over the for RNA folding, catalysis, subunit association, correlated evolution, broad course of ribosomal evolution. -
Structures and Stabilization of Kinetoplastid-Specific Split Rrnas Revealed by Comparing Leishmanial and Human Ribosomes
ARTICLE Received 7 Jun 2016 | Accepted 13 Sep 2016 | Published 18 Oct 2016 DOI: 10.1038/ncomms13223 OPEN Structures and stabilization of kinetoplastid-specific split rRNAs revealed by comparing leishmanial and human ribosomes Xing Zhang1,2,*, Mason Lai3,*, Winston Chang3, Iris Yu3, Ke Ding3, Jan Mrazek4,HweeL.Ng4, Otto O. Yang2,4, Dmitri A. Maslov5 & Z. Hong Zhou2,3 The recent success in ribosome structure determination by cryoEM has opened the door to defining structural differences between ribosomes of pathogenic organisms and humans and to understand ribosome-targeting antibiotics. Here, by direct electron-counting cryoEM, we have determined the structures of the Leishmania donovani and human ribosomes at 2.9 Å and 3.6 Å, respectively. Our structure of the leishmanial ribosome elucidates the organization of the six fragments of its large subunit rRNA (as opposed to a single 28S rRNA in most eukaryotes, including humans) and reveals atomic details of a unique 20 amino acid extension of the uL13 protein that pins down the ends of three of the rRNA fragments. The structure also fashions many large rRNA expansion segments. Direct comparison of our human and leishmanial ribosome structures at the decoding A-site sheds light on how the bacterial ribosome-targeting drug paromomycin selectively inhibits the eukaryotic L. donovani, but not human, ribosome. 1 Center of Cryo Electron Microscopy, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. 2 California NanoSystems Institute, University of California, Los Angeles, California 90095, USA. 3 Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA. 4 Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA. -
Ribosomal DNA Copy Number Is Coupled with Gene Expression Variation and Mitochondrial Abundance in Humans
ARTICLE Received 12 Apr 2014 | Accepted 30 Jul 2014 | Published 11 Sep 2014 DOI: 10.1038/ncomms5850 Ribosomal DNA copy number is coupled with gene expression variation and mitochondrial abundance in humans John G. Gibbons1, Alan T. Branco1, Shoukai Yu1 & Bernardo Lemos1 Ribosomes are essential intracellular machines composed of proteins and RNA molecules. The DNA sequences (rDNA) encoding ribosomal RNAs (rRNAs) are tandemly repeated and give origin to the nucleolus. Here we develop a computational method for estimating rDNA dosage (copy number) and mitochondrial DNA abundance using whole-genome short-read DNA sequencing. We estimate these attributes across hundreds of human genomes and their association with global gene expression. The analyses uncover abundant variation in rDNA dosage that is coupled with the expression of hundreds of functionally coherent gene sets. These include associations with genes coding for chromatin components that target the nucleolus, including CTCF and HP1b. Finally, the data show an inverse association between rDNA dosage and mitochondrial DNA abundance that is manifested across genotypes. Our findings uncover a novel and cryptic source of hypervariable genomic diversity with global regulatory consequences (ribosomal eQTL) in humans. The variation provides a mechanism for cellular homeostasis and for rapid and reversible adaptation. 1 Program in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Building 2, Room 219, Boston, Massachusetts 02115, USA. Correspondence and requests for materials should be addressed to B.L. (email: [email protected]). NATURE COMMUNICATIONS | 5:4850 | DOI: 10.1038/ncomms5850 | www.nature.com/naturecommunications 1 & 2014 Macmillan Publishers Limited. -
HUMAN RIBOSOME BIOGENESIS and the REGULATION of the TUMOUR SUPPRESSOR P53
HUMAN RIBOSOME BIOGENESIS AND THE REGULATION OF THE TUMOUR SUPPRESSOR p53 Andria Pelava Submitted for Doctor of Philosophy Final submission: December 2016 Institute of Cell and Molecular Biosciences Faculty of Medical Sciences Newcastle University ii Abstract Ribosome production is an energetically expensive and, therefore, highly regulated process. Defects in ribosome biogenesis lead to genetic diseases called Ribosomopathies, such as Dyskeratosis Congenita (DC), and mutations in ribosomal proteins and ribosome biogenesis factors are linked to multiple types of cancer. During ribosome biogenesis, the ribosomal RNAs (rRNAs) are processed and modified, and defects in ribosome biogenesis lead to the activation of p53. This project aimed to investigate the functions of Dyskerin, mutated in X-linked DC, in human ribosome biogenesis and p53 regulation, and to explore the link between ribosome production and p53 homeostasis. Dyskerin is an rRNA pseudouridine synthase and required for telomere maintenance. There is some debate as to whether DC is the result of telomere maintenance or ribosome biogenesis defects. It is shown here that human Dyskerin is required for the production of both LSU and SSU, and knockdown of Dyskerin leads to p53 activation via inhibition of MDM2 via the 5S RNP, an LSU assembly intermediate which accumulates after ribosome biogenesis defects. My data indicate that p53 activation, due to defects in ribosome biogenesis, may contribute to the clinical symptoms seen in patients suffering with DC. In addition, it is shown that defects in early or late stages of SSU or LSU biogenesis, result in activation of p53 via the 5S RNP-MDM2 pathway, and that p53 is induced in less than 12 hours after ribosome biogenesis defects. -
Fanconi Anemia Protein FANCI Functions in Ribosome Biogenesis
Fanconi anemia protein FANCI functions in ribosome biogenesis Samuel B. Sondallea, Simonne Longerichb,1, Lisa M. Ogawab, Patrick Sungb,c, and Susan J. Basergaa,b,c,2 aDepartment of Genetics, Yale School of Medicine, New Haven, CT 06520; bDepartment of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520; and cDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520 Edited by Joseph G. Gall, Carnegie Institution of Washington, Baltimore, MD, and approved December 28, 2018 (received for review July 8, 2018) Fanconi anemia (FA) is a disease of DNA repair characterized by bone responsible for the transcription of pre-ribosomal RNA (pre- marrow failure and a reduced ability to remove DNA interstrand rRNA) (33). The clear phenotypic overlap between FA and cross-links. Here, we provide evidence that the FA protein FANCI also bone marrow failure ribosomopathies and the connection between functions in ribosome biogenesis, the process of making ribosomes BRCA1 (FANCS) and RNAPI suggest a possible connection be- that initiates in the nucleolus. We show that FANCI localizes to the tween FA and defects in ribosome biogenesis. nucleolus and is functionally and physically tied to the transcription The process of making ribosomes in eukaryotes, termed ri- of pre-ribosomal RNA (pre-rRNA) and to large ribosomal subunit bosome biogenesis, initiates in the large nonmembrane-bound (LSU) pre-rRNA processing independent of FANCD2. While FANCI is nuclear organelle, the nucleolus (NO) (34, 35). In the NO, tan- known to be monoubiquitinated when activated for DNA repair, we dem repeats of ribosomal DNA (rDNA) (36) are transcribed by find that it is predominantly in the deubiquitinated state in the RNAPI, which generates a long pre-rRNA (37). -
Transcriptomic Regulation of Alternative Phenotypic Trajectories in Embryos of the Annual Killifish Austrofundulus Limnaeus
Portland State University PDXScholar Dissertations and Theses Dissertations and Theses Fall 11-30-2017 Transcriptomic Regulation of Alternative Phenotypic Trajectories in Embryos of the Annual Killifish Austrofundulus limnaeus Amie L. Romney Portland State University Follow this and additional works at: https://pdxscholar.library.pdx.edu/open_access_etds Part of the Biology Commons, and the Genetics and Genomics Commons Let us know how access to this document benefits ou.y Recommended Citation Romney, Amie L., "Transcriptomic Regulation of Alternative Phenotypic Trajectories in Embryos of the Annual Killifish Austrofundulus limnaeus" (2017). Dissertations and Theses. Paper 4033. https://doi.org/10.15760/etd.5917 This Dissertation is brought to you for free and open access. It has been accepted for inclusion in Dissertations and Theses by an authorized administrator of PDXScholar. Please contact us if we can make this document more accessible: [email protected]. Transcriptomic Regulation of Alternative Phenotypic Trajectories in embryos of the Annual Killifish Austrofundulus limnaeus by Amie Lynn Thomas Romney A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biology Dissertation Committee Jason Podrabsky, Chair Suzanne Estes Bradley Buckley Todd Rosenstiel Dirk Iwata-Reuyl Portland State University 2017 © 2017 Amie Lynn Thomas Romney ABSTRACT The Annual Killifish, Austrofundulus limnaeus, survives the seasonal drying of their pond habitat in the form of embryos entering diapause midway through development. The diapause trajectory is one of two developmental phenotypes. Alternatively, individuals can “escape” entry into diapause and develop continuously until hatching. The alternative phenotypes of A. limnaeus are a form of developmental plasticity that provides this species with a physiological adaption for surviving stressful environments. -
An Update on Mitochondrial Ribosome Biology: the Plant Mitoribosome in the Spotlight
cells Review An Update on Mitochondrial Ribosome Biology: The Plant Mitoribosome in the Spotlight Artur Tomal y , Malgorzata Kwasniak-Owczarek y and Hanna Janska * Department of Cellular Molecular Biology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland; [email protected] (A.T.); [email protected] (M.K.-O.) * Correspondence: [email protected]; Tel.: +0048-713-756-249; Fax: +0048-713-756-234 These authors contributed equally to this work. y Received: 31 October 2019; Accepted: 1 December 2019; Published: 3 December 2019 Abstract: Contrary to the widely held belief that mitochondrial ribosomes (mitoribosomes) are highly similar to bacterial ones, recent experimental evidence reveals that mitoribosomes do differ significantly from their bacterial counterparts. This review is focused on plant mitoribosomes, but we also highlight the most striking similarities and differences between the plant and non-plant mitoribosomes. An analysis of the composition and structure of mitoribosomes in trypanosomes, yeast, mammals and plants uncovers numerous organism-specific features. For the plant mitoribosome, the most striking feature is the enormous size of the small subunit compared to the large one. Apart from the new structural information, possible functional peculiarities of different types of mitoribosomes are also discussed. Studies suggest that the protein composition of mitoribosomes is dynamic, especially during development, giving rise to a heterogeneous populations of ribosomes fulfilling specific functions. Moreover, convincing data shows that mitoribosomes interact with components involved in diverse mitochondrial gene expression steps, forming large expressosome-like structures. Keywords: mitochondrial ribosome; ribosomal proteins; ribosomal rRNA; PPR proteins; translation; plant mitoribosome 1. -
Supersized Ribosomal RNA Expansion Segments in Asgard Archaea 2 Authors: Petar I
bioRxiv preprint doi: https://doi.org/10.1101/2019.12.25.888164; this version posted June 13, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Supersized ribosomal RNA expansion segments in Asgard archaea 2 Authors: Petar I. Penev1,2, Sara Fakhretaha-Aval1,3, Vaishnavi J. Patel4, Jamie J. Cannone4, 3 Robin R. Gutell4, Anton S. Petrov1,3*, Loren Dean Williams1,2,3*, Jennifer B. Glass1,2,5* 4 Affiliations: 1NASA Center for the Origin of Life, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA 2School of Biological Sciences, Georgia Institute of Technology, North Avenue, Atlanta, GA 30332, USA 3School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Dr, Atlanta, GA 30332, USA 5 4Department of Integrative Biology, The University of Texas at Austin, 2415 Speedway #C0930, 6 Austin, TX 78712, USA 7 5School of Earth and Atmospheric Sciences, Georgia Institute of Technology, 311 Ferst Dr, 8 Atlanta, GA 30332, USA 9 *Correspondence to: [email protected]; [email protected]; 10 [email protected] 11 1 bioRxiv preprint doi: https://doi.org/10.1101/2019.12.25.888164; this version posted June 13, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. -
Structures and Stabilization of Kinetoplastid-Specific Split Rrnas
ARTICLE Received 7 Jun 2016 | Accepted 13 Sep 2016 | Published 18 Oct 2016 DOI: 10.1038/ncomms13223 OPEN Structures and stabilization of kinetoplastid-specific split rRNAs revealed by comparing leishmanial and human ribosomes Xing Zhang1,2,*, Mason Lai3,*, Winston Chang3, Iris Yu3, Ke Ding3, Jan Mrazek4,HweeL.Ng4, Otto O. Yang2,4, Dmitri A. Maslov5 & Z. Hong Zhou2,3 The recent success in ribosome structure determination by cryoEM has opened the door to defining structural differences between ribosomes of pathogenic organisms and humans and to understand ribosome-targeting antibiotics. Here, by direct electron-counting cryoEM, we have determined the structures of the Leishmania donovani and human ribosomes at 2.9 Å and 3.6 Å, respectively. Our structure of the leishmanial ribosome elucidates the organization of the six fragments of its large subunit rRNA (as opposed to a single 28S rRNA in most eukaryotes, including humans) and reveals atomic details of a unique 20 amino acid extension of the uL13 protein that pins down the ends of three of the rRNA fragments. The structure also fashions many large rRNA expansion segments. Direct comparison of our human and leishmanial ribosome structures at the decoding A-site sheds light on how the bacterial ribosome-targeting drug paromomycin selectively inhibits the eukaryotic L. donovani, but not human, ribosome. 1 Center of Cryo Electron Microscopy, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. 2 California NanoSystems Institute, University of California, Los Angeles, California 90095, USA. 3 Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA. 4 Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA. -
The Ribosomal Protein Genes and Minute Loci of Drosophila
Open Access Research2007MarygoldetVolume al. 8, Issue 10, Article R216 The ribosomal protein genes and Minute loci of Drosophila melanogaster Steven J Marygold*, John Roote†, Gunter Reuter‡, Andrew Lambertsson§, Michael Ashburner†, Gillian H Millburn†, Paul M Harrison¶, Zhan Yu¶, Naoya Kenmochi¥, Thomas C Kaufman#, Sally J Leevers* and Kevin R Cook# Addresses: *Growth Regulation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields, London WC2A 3PX, UK. †Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK. ‡Institute of Genetics, Biologicum, Martin Luther University Halle-Wittenberg, Weinbergweg, Halle D-06108, Germany. §Institute of Molecular Biosciences, University of Oslo, Blindern, Olso N-0316, Norway. ¶Department of Biology, McGill University, Dr Penfield Ave, Montreal, Quebec H3A 1B1, Canada. ¥Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. #Department of Biology, Indiana University, E. Third Street, Bloomington, IN 47405-7005, USA. Correspondence: Steven J Marygold. Email: [email protected]. Kevin R Cook. Email: [email protected] Published: 10 October 2007 Received: 17 June 2007 Revised: 10 October 2007 Genome Biology 2007, 8:R216 (doi:10.1186/gb-2007-8-10-r216) Accepted: 10 October 2007 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2007/8/10/R216 © 2007 Marygold et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.