Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

Title: The Structure of a Rigorously Conserved RNA Element within the SARS Virus Genome

Journal Article · · PLoS Biology (Online)
 [1];  [2];  [3];  [3];  [2];  [1]
  1. Univ. of California, Santa Cruz, CA (United States). The Center for the Molecular Biology of RNA; Univ. of California, Santa Cruz, CA (United States). Dept. of Chemistry and Biochemistry
  2. Univ. of California, Santa Cruz, CA (United States). The Center for the Molecular Biology of RNA; Univ. of California, Santa Cruz, CA (United States). Dept. of Molecular, Cell and Developmental Biology
  3. Univ. of California, Santa Cruz, CA (United States). The Center for the Molecular Biology of RNA; Univ. of California, Santa Cruz, CA (United States). Howard Hughes Medical Inst. and Dept. of Biomolecular Engineering
+ Show Author Affiliations

We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m) RNA element of the SARS virus genome to 2.7-Å resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 39 end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigorous sequence conservation in an otherwise rapidly mutable RNA genome. We find that this extreme conservation is clearly explained by the requirement to form a highly structured RNA whose unique tertiary structure includes a sharp 908 kink of the helix axis and several novel longer-range tertiary interactions. The tertiary base interactions create a tunnel that runs perpendicular to the main helical axis whose interior is negatively charged and binds two magnesium ions. These unusual features likely form interaction surfaces with conserved host cell components or other reactive sites required for virus function. Based on its conservation in viral pathogen genomes and its absence in the human genome, we suggest that these unusual structural features in the s2m RNA element are attractive targets for the design of anti-viral therapeutic agents. Structural genomics has sought to deduce protein function based on three-dimensional homology. Here we have extended this approach to RNA by proposing potential functions for a rigorously conserved set of RNA tertiary structural interactions that occur within the SARS RNA genome itself. Based on tertiary structural comparisons, we propose the s2m RNA binds one or more proteins possessing an oligomer-binding-like fold, and we suggest a possible mechanism for SARS viral RNA hijacking of host protein synthesis, both based upon observed s2m RNA macromolecular mimicry of a relevant ribosomal RNA fold.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
1627133
Journal Information:
PLoS Biology (Online), Vol. 3, Issue 1; ISSN 1545-7885
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (51)

Structural genomics of the SARS coronavirus: cloning, expression, crystallization and preliminary crystallographic study of the Nsp9 protein journal August 2003
G-quartet-dependent recognition between the FMRP RGG box and RNA journal October 2003
Refinement of Macromolecular Structures by the Maximum-Likelihood Method journal May 1997
Common and distinctive features of GNRA tetraloops based on a GUAA tetraloop structure at 1.4 A resolution journal March 2003
The structure of the translational initiation factor IF1 from E.coli contains an oligomer-binding motif journal March 1997
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination journal September 1998
X-ray analysis of an RNA tetraplex (UGGGGU)4 with divalent Sr2+ ions at subatomic resolution (0.61 A) journal November 2001
Improved methods for building protein models in electron density maps and the location of errors in these models journal March 1991
Solution structure of an unusually stable RNA tetraplex containing G- and U-quartet structures journal September 1992
A common RNA motif in the 3' end of the genomes of astroviruses, avian infectious bronchitis virus and an equine rhinovirus. journal April 1998
The CCP4 suite programs for protein crystallography journal September 1994
Structure-based assignment of the biochemical function of a hypothetical protein: A test case of structural genomics journal December 1998
Metal binding and base ionization in the U6 RNA intramolecular stem-loop structure journal May 2002
Structure of the 30S ribosomal subunit journal September 2000
The nsp9 Replicase Protein of SARS-Coronavirus, Structure and Functional Insights journal February 2004
Crystal Structure of the Ribonucleoprotein Core of the Signal Recognition Particle journal February 2000
Crystal Structure of an Initiation Factor Bound to the 30S Ribosomal Subunit journal January 2001
The Genome Sequence of the SARS-Associated Coronavirus journal May 2003
Structural features that give rise to the unusual stability of RNA hairpins containing GNRA loops journal July 1991
Characterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome journal May 2003
Crystal Structure of an RNA Purine-Rich Tetraplex Containing Adenine Tetrads journal July 2003
Hijacking the translation apparatus by RNA viruses journal August 2002
Structure of the ternary complex of EF-Tu: macromolecular mimicry in translation journal March 1996
A Single Internal Ribosome Entry Site Containing a G Quartet RNA Structure Drives Fibroblast Growth Factor 2 Gene Expression at Four Alternative Translation Initiation Codons journal October 2003
Pattern searching/alignment with RNA primary and secondary structures: an effective descriptor for tRNA journal January 1990
Macromolecular mimicry journal February 2000
Structure of a natural guanine-responsive riboswitch complexed with the metabolite hypoxanthine journal November 2004
Lethal and temperature-sensitive mutations and their suppressors identify an essential structural element in U2 small nuclear RNA. journal December 1990
Structural genomics of RNA journal November 2000
Quantitative analysis of nucleic acid three-dimensional structures journal May 2001
The role of mRNA 5′-noncoding and 3′-end sequences on 40S ribosomal subunit recruitment, and how RNA viruses successfully compete with cellular mRNAs to ensure their own protein synthesis journal May 2003
The eIF1A Solution Structure Reveals a Large RNA-Binding Surface Important for Scanning Function journal January 2000
Crystal Structure of a Bulged RNA Tetraplex at 1.1 Å Resolution journal November 2003
The severe acute respiratory syndrome-coronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world journal March 2004
An overview of the CCP4 project in protein crystallography: an example of a collaborative project journal December 2002
RNA Tertiary Structure Mediation by Adenosine Platforms journal September 1996
Searching for patterns in genomic data journal December 1997
Crystal structure of the Ffh and EF-G binding sites in the conserved domain IV of Escherichia coli 4.5S RNA journal May 2000
Ribosomal Proteins S12 and S13 Function as Control Elements for Translocation of the mRNA:tRNA Complex journal August 2003
Structure of a natural guanine-responsive riboswitch complexed with the metabolite hypoxanthine journal November 2004
Metal binding and base ionization in the U6 RNA intramolecular stem-loop structure journal May 2002
The severe acute respiratory syndrome-coronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world journal March 2004
Structure-based assignment of the biochemical function of a hypothetical protein: A test case of structural genomics journal December 1998
Interaction of Human Nuclear Topoisomerase I with Guanosine Quartet-forming and Guanosine-rich Single-stranded DNA and RNA Oligonucleotides journal March 2002
Pattern searching/alignment with RNA primary and secondary structures: an effective descriptor for tRNA journal January 1990
The structure of the translational initiation factor IF1 from E.coli contains an oligomer-binding motif journal March 1997
A common RNA motif in the 3' end of the genomes of astroviruses, avian infectious bronchitis virus and an equine rhinovirus. journal April 1998
Crystal Structure of an Initiation Factor Bound to the 30S Ribosomal Subunit journal January 2001
Structural features that give rise to the unusual stability of RNA hairpins containing GNRA loops journal July 1991
Visualizing the Logic Behind RNA Self-Assembly journal September 1996
Common and distinctive features of GNRA tetraloops based on a GUAA tetraloop structure at 1.4 A resolution journal March 2003

Cited By (18)

Molecular identification and characterization of novel coronaviruses infecting graylag geese (Anser anser), feral pigeons (Columbia livia) and mallards (Anas platyrhynchos) journal June 2005
Distribution and Evolutionary History of the Mobile Genetic Element s2m in Coronaviruses journal July 2016
Blind prediction of noncanonical RNA structure at atomic accuracy journal May 2018
The GA-minor submotif as a case study of RNA modularity, prediction, and design: RNA modularity, prediction, and design journal February 2013
Minimal RNA Aptamer Sequences That Can Inhibit or Alleviate Noncompetitive Inhibition of the Muscle-Type Nicotinic Acetylcholine Receptor journal January 2010
Blind prediction of noncanonical RNA structure at atomic accuracy journal February 2018
FARFAR2: Improved de novo Rosetta prediction of complex global RNA folds journal September 2019
Visualization of macromolecular structures journal March 2010
RNA Recognition and Cleavage by the SARS Coronavirus Endoribonuclease journal August 2006
Structure of the SARS Coronavirus Nucleocapsid Protein RNA-binding Dimerization Domain Suggests a Mechanism for Helical Packaging of Viral RNA journal May 2007
Variable Oligomerization Modes in Coronavirus Non-structural Protein 9 journal November 2008
RNA structure analysis of alphacoronavirus terminal genome regions journal December 2014
Visualization of macromolecular structures journal March 2010
A recurrent magnesium-binding motif provides a framework for the ribosomal peptidyl transferase center journal March 2009
Blind prediction of noncanonical RNA structure at atomic accuracy journal May 2018
A mobile genetic element with unknown function found in distantly related viruses journal April 2013
Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies journal April 2005
Screening of Feral and Wood Pigeons for Viruses Harbouring a Conserved Mobile Viral Element: Characterization of Novel Astroviruses and Picornaviruses journal October 2011

Similar Records

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology
Life Sciences & Biomedicine - Other Topics