RNA G-Quadruplexes in the model plant species Arabidopsis thaliana: prevalence and possible functional roles

Tandem stretches of guanines can associate in hydrogen-bonded arrays to form G-quadruplexes, which are stabilized by K+ ions. Using computational methods, we searched for G-Quadruplex Sequence (GQS) patterns in the model plant species Arabidopsis thaliana. We found ∼1200 GQS with a G3 repeat sequence motif, most of which are located in the intergenic region. Using a Markov modeled genome, we determined that GQS are significantly underrepresented in the genome. Additionally, we found ∼43 000 GQS with a G2 repeat sequence motif; notably, 80% of these were located in genic regions, suggesting that these sequences may fold at the RNA level. Gene Ontology functional analysis revealed that GQS are overrepresented in genes encoding proteins of certain functional categories, including enzyme activity. Conversely, GQS are underrepresented in other categories of genes, notably those for non-coding RNAs such as tRNAs and rRNAs. We also find that genes that are differentially regulated by drought are significantly more likely to contain a GQS. CD-detected K+ titrations performed on representative RNAs verified formation of quadruplexes at physiological K+ concentrations. Overall, this study indicates that GQS are present at unique locations in Arabidopsis and that folding of RNA GQS may play important roles in regulating gene expression.

[1]  M. Borgognone,et al.  Cellular nucleic-acid-binding protein, a transcriptional enhancer of c-Myc, promotes the formation of parallel G-quadruplexes. , 2010, The Biochemical journal.

[2]  Ann E Loraine,et al.  Prevalence of alternative splicing choices in Arabidopsis thaliana , 2010, BMC Plant Biology.

[3]  Manikandan Paramasivam,et al.  The KRAS Promoter Responds to Myc-associated Zinc Finger and Poly(ADP-ribose) Polymerase 1 Proteins, Which Recognize a Critical Quadruplex-forming GA-element* , 2010, The Journal of Biological Chemistry.

[4]  Sai Guna Ranjan Gurazada,et al.  Genome sequencing and analysis of the model grass Brachypodium distachyon , 2010, Nature.

[5]  Naoki Sugimoto,et al.  Molecular crowding of the cosolutes induces an intramolecular i-motif structure of triplet repeat DNA oligomers at neutral pH. , 2010, Chemical communications.

[6]  T. Sakurai,et al.  Genome sequence of the palaeopolyploid soybean , 2010, Nature.

[7]  Manikandan Paramasivam,et al.  Cellular uptake and binding of guanidine-modified phthalocyanines to KRAS/HRAS G-quadruplexes. , 2010, Chemical communications.

[8]  Dawn H. Nagel,et al.  The B73 Maize Genome: Complexity, Diversity, and Dynamics , 2009, Science.

[9]  C. Hodgman,et al.  Repression of translation of human estrogen receptor alpha by G-quadruplex formation. , 2009, Biochemistry.

[10]  R. Bambara,et al.  A Recombination Hot Spot in HIV-1 Contains Guanosine Runs That Can Form a G-quartet Structure and Promote Strand Transfer in Vitro* , 2009, The Journal of Biological Chemistry.

[11]  A. Benz,et al.  A comparison of DNA and RNA quadruplex structures and stabilities. , 2009, Bioorganic & medicinal chemistry.

[12]  Yiqiang Zhao,et al.  Genome-wide colonization of gene regulatory elements by G4 DNA motifs , 2009, Nucleic acids research.

[13]  Markus Wieland,et al.  Predictable suppression of gene expression by 5′-UTR-based RNA quadruplexes , 2009, Nucleic acids research.

[14]  Daekyu Sun,et al.  Identification and Characterization of Nucleolin as a c-myc G-quadruplex-binding Protein* , 2009, The Journal of Biological Chemistry.

[15]  S. Basu,et al.  An unusually stable G-quadruplex within the 5'-UTR of the MT3 matrix metalloproteinase mRNA represses translation in eukaryotic cells. , 2009, Biochemistry.

[16]  H. Nakagama,et al.  Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter: implications for transcription , 2009, Nucleic acids research.

[17]  V. K. Yadav,et al.  Evidence of genome-wide G4 DNA-mediated gene expression in human cancer cells , 2009, Nucleic acids research.

[18]  Mihaela M. Martis,et al.  The Sorghum bicolor genome and the diversification of grasses , 2009, Nature.

[19]  Imrich Géci,et al.  Identification of a new G-quadruplex motif in the KRAS promoter and design of pyrene-modified G4-decoys with antiproliferative activity in pancreatic cancer cells. , 2009, Journal of medicinal chemistry.

[20]  S. Balasubramanian,et al.  Position and stability are determining factors for translation repression by an RNA G-quadruplex-forming sequence within the 5' UTR of the NRAS proto-oncogene. , 2008, Biochemistry.

[21]  Ram Krishna Thakur,et al.  Metastases suppressor NM23-H2 interaction with G-quadruplex DNA within c-MYC promoter nuclease hypersensitive element induces c-MYC expression , 2008, Nucleic acids research.

[22]  Julian Leon Huppert,et al.  G-quadruplexes: the beginning and end of UTRs , 2008, Nucleic acids research.

[23]  S. Maiti,et al.  Role of molecular crowding in perturbing quadruplex-Watson Crick duplex equilibrium. , 2008, Nucleic acids symposium series.

[24]  Masakazu Satou,et al.  Arabidopsis transcriptome analysis under drought, cold, high-salinity and ABA treatment conditions using a tiling array. , 2008, Plant & cell physiology.

[25]  N. Smargiasso,et al.  G-quadruplex DNA assemblies: loop length, cation identity, and multimer formation. , 2008, Journal of the American Chemical Society.

[26]  V. Scaria,et al.  Inhibition of translation in living eukaryotic cells by an RNA G-quadruplex motif. , 2008, RNA.

[27]  H. Mori,et al.  Genome Structure of the Legume, Lotus japonicus , 2008, DNA research : an international journal for rapid publication of reports on genes and genomes.

[28]  S. Balasubramanian,et al.  Exploring the differential recognition of DNA G-quadruplex targets by small molecules using dynamic combinatorial chemistry. , 2008, Angewandte Chemie.

[29]  M. Teulade‐Fichou,et al.  A hitchhiker's guide to G-quadruplex ligands. , 2008, Organic & biomolecular chemistry.

[30]  J. Bennetzen,et al.  The Physcomitrella Genome Reveals Evolutionary Insights into the Conquest of Land by Plants , 2008, Science.

[31]  P. Bolton,et al.  Circular dichroism of quadruplex DNAs: applications to structure, cation effects and ligand binding. , 2007, Methods.

[32]  Oleg Kikin,et al.  GRSDB2 and GRS_UTRdb: databases of quadruplex forming G-rich sequences in pre-mRNAs and mRNAs , 2007, Nucleic Acids Res..

[33]  Tanya Z. Berardini,et al.  The Arabidopsis Information Resource (TAIR): gene structure and function annotation , 2007, Nucleic Acids Res..

[34]  L. Hurley,et al.  Characterization of the G-quadruplexes in the duplex nuclease hypersensitive element of the PDGF-A promoter and modulation of PDGF-A promoter activity by TMPyP4 , 2007, Nucleic acids research.

[35]  C. Azzalin,et al.  Telomeric Repeat–Containing RNA and RNA Surveillance Factors at Mammalian Chromosome Ends , 2007, Science.

[36]  Shantanu Chowdhury,et al.  QuadBase: genome-wide database of G4 DNA—occurrence and conservation in human, chimpanzee, mouse and rat promoters and 146 microbes , 2007, Nucleic Acids Res..

[37]  Michael L. Creech,et al.  Integration of biological networks and gene expression data using Cytoscape , 2007, Nature Protocols.

[38]  J. Poulain,et al.  The grapevine genome sequence suggests ancestral hexaploidization in major angiosperm phyla , 2007, Nature.

[39]  Samer Khateb,et al.  The tetraplex (CGG)n destabilizing proteins hnRNP A2 and CBF-A enhance the in vivo translation of fragile X premutation mRNA , 2007, Nucleic acids research.

[40]  Markus Wieland,et al.  RNA quadruplex-based modulation of gene expression. , 2007, Chemistry & biology.

[41]  A. Reddy.  Alternative splicing of pre-messenger RNAs in plants in the genomic era. , 2007, Annual review of plant biology.

[42]  Shankar Balasubramanian,et al.  An RNA G-quadruplex in the 5' UTR of the NRAS proto-oncogene modulates translation. , 2007, Nature chemical biology.

[43]  A. Reddy,et al.  Alternative splicing of pre-mRNAs of Arabidopsis serine/arginine-rich proteins: regulation by hormones and stresses. , 2007, The Plant journal : for cell and molecular biology.

[44]  Shankar Balasubramanian,et al.  G-quadruplexes in promoters throughout the human genome , 2006, Nucleic acids research.

[45]  John A. Hamilton,et al.  The TIGR Rice Genome Annotation Resource: improvements and new features , 2006, Nucleic Acids Res..

[46]  B. Roe,et al.  Legume genome evolution viewed through the Medicago truncatula and Lotus japonicus genomes , 2006, Proceedings of the National Academy of Sciences.

[47]  Sarah W. Burge,et al.  Quadruplex DNA: sequence, topology and structure , 2006, Nucleic acids research.

[48]  M. Gribskov,et al.  The Genome of Black Cottonwood, Populus trichocarpa (Torr. & Gray) , 2006, Science.

[49]  N. Sugimoto,et al.  Hydration regulates thermodynamics of G-quadruplex formation under molecular crowding conditions. , 2006, Journal of the American Chemical Society.

[50]  R. Shafer,et al.  Engineering the quadruplex fold: nucleoside conformation determines both folding topology and molecularity in guanine quadruplexes. , 2006, Journal of the American Chemical Society.

[51]  Mitali Mukerji,et al.  Genome-wide prediction of G4 DNA as regulatory motifs: role in Escherichia coli global regulation. , 2006, Genome research.

[52]  G. Parkinson,et al.  Predictive modelling of topology and loop variations in dimeric DNA quadruplex structures , 2006, Nucleic acids research.

[53]  Patrick Achard,et al.  Integration of Plant Responses to Environmentally Activated Phytohormonal Signals , 2006, Science.

[54]  S. Maiti,et al.  The effect of osmolytes and small molecule on Quadruplex–WC duplex equilibrium: a fluorescence resonance energy transfer study , 2005, Nucleic acids research.

[55]  Paul Gollnick,et al.  Complexity in regulation of tryptophan biosynthesis in Bacillus subtilis. , 2005, Annual review of genetics.

[56]  Martin Kuiper,et al.  BiNGO: a Cytoscape plugin to assess overrepresentation of Gene Ontology categories in Biological Networks , 2005, Bioinform..

[57]  Takuji Sasaki,et al.  The map-based sequence of the rice genome , 2005, Nature.

[58]  Mahadeb Pal,et al.  The role of the transcription bubble and TFIIB in promoter clearance by RNA polymerase II. , 2005, Molecular cell.

[59]  R. Breaker,et al.  Riboswitches as versatile gene control elements. , 2005, Current opinion in structural biology.

[60]  Shankar Balasubramanian,et al.  Prevalence of quadruplexes in the human genome , 2005, Nucleic acids research.

[61]  S. Neidle,et al.  Highly prevalent putative quadruplex sequence motifs in human DNA , 2005, Nucleic acids research.

[62]  B. Roe,et al.  Sequencing the Genespaces of Medicago truncatula and Lotus japonicus1 , 2005, Plant Physiology.

[63]  Stephen Neidle,et al.  Loop-length-dependent folding of G-quadruplexes. , 2004, Journal of the American Chemical Society.

[64]  N. Sugimoto,et al.  Duplex dissociation of telomere DNAs induced by molecular crowding. , 2004, Journal of the American Chemical Society.

[65]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[66]  Joseph M. Dale,et al.  Empirical Analysis of Transcriptional Activity in the Arabidopsis Genome , 2003, Science.

[67]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

[68]  Eric S. Lander,et al.  The mosaic structure of variation in the laboratory mouse genome , 2002, Nature.

[69]  N. Sugimoto,et al.  Molecular crowding regulates the structural switch of the DNA G-quadruplex. , 2002, Biochemistry.

[70]  D. Bearss,et al.  Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[71]  Huanming Yang,et al.  A Draft Sequence of the Rice Genome (Oryza sativa L. ssp. japonica) , 2002, Science.

[72]  Huanming Yang,et al.  A Draft Sequence of the Rice Genome (Oryza sativa L. ssp. indica) , 2002, Science.

[73]  N. Eckardt.  Alternative Splicing and the Control of Flowering Time , 2002, The Plant Cell Online.

[74]  J. Darnell,et al.  Fragile X Mental Retardation Protein Targets G Quartet mRNAs Important for Neuronal Function , 2001, Cell.

[75]  C. Ehresmann,et al.  The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif , 2001, The EMBO journal.

[76]  E. Blumwald,et al.  Transgenic salt-tolerant tomato plants accumulate salt in foliage but not in fruit , 2001, Nature Biotechnology.

[77]  T. Sosnick.  Characterization of Tertiary Folding of RNA by Circular Dichroism and Urea , 2001, Current protocols in nucleic acid chemistry.

[78]  R. Leigh.  Potassium homeostasis and membrane transport , 2001 .

[79]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[80]  Stephen M. Mount,et al.  The genome sequence of Drosophila melanogaster. , 2000, Science.

[81]  Howard M. Goodman,et al.  The Arabidopsis splicing factor SR1 is regulated by alternative splicing , 2000, Plant Molecular Biology.

[82]  N. Proudfoot,et al.  Specific transcriptional pausing activates polyadenylation in a coupled in vitro system. , 1999, Molecular cell.

[83]  Jean-Louis Mergny,et al.  Following G‐quartet formation by UV‐spectroscopy , 1998, FEBS letters.

[84]  J. Feigon,et al.  The selectivity for K+ versus Na+ in DNA quadruplexes is dominated by relative free energies of hydration: a thermodynamic analysis by 1H NMR. , 1996, Biochemistry.

[85]  H. Deng,et al.  Duplex to quadruplex equilibrium of the self‐complementary oligonucleotide d(GGGGCCCC) , 1995, Biopolymers.

[86]  W. Sundquist,et al.  Evidence for interstrand quadruplex formation in the dimerization of human immunodeficiency virus 1 genomic RNA. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[87]  J. Feigon,et al.  Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[88]  S. Swaminathan,et al.  A DNA aptamer which binds to and inhibits thrombin exhibits a new structural motif for DNA. , 1993, Biochemistry.

[89]  E. Vermaas,et al.  Selection of single-stranded DNA molecules that bind and inhibit human thrombin , 1992, Nature.

[90]  H. Goodman,et al.  The centromere region of Arabidopsis thaliana chromosome 1 contains telomere-similar sequences. , 1991, Nucleic acids research.

[91]  T. Cech,et al.  Monovalent cation-induced structure of telomeric DNA: The G-quartet model , 1989, Cell.

[92]  D. Inzé,et al.  Characterization of highly repetitive sequences of Arabidopsis thaliana. , 1988, Nucleic acids research.

[93]  R. Leigh,et al.  A HYPOTHESIS RELATING CRITICAL POTASSIUM CONCENTRATIONS FOR GROWTH TO THE DISTRIBUTION AND FUNCTIONS OF THIS ION IN THE PLANT CELL , 1984 .

[94]  Wolfram Saenger,et al.  Principles of Nucleic Acid Structure , 1983 .

[95]  C. Cantor,et al.  Biophysical Chemistry: Part II: Techniques for the Study of Biological Structure and Function , 1980 .

[96]  R. Munns,et al.  Mechanisms of salt tolerance in nonhalophytes. , 1980 .

[97]  D. Davies,et al.  Helix formation by guanylic acid. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[98]  M. Kimmel,et al.  Conflict of interest statement. None declared. , 2010 .

[99]  Jian Wang,et al.  BGI-RIS: an integrated information resource and comparative analysis workbench for rice genomics , 2004, Nucleic Acids Res..

[100]  R. Shafer,et al.  Biological aspects of DNA/RNA quadruplexes , 2000, Biopolymers.

[101]  F. Nielsen,et al.  A guanosine quadruplex and two stable hairpins flank a major cleavage site in insulin-like growth factor II mRNA. , 1994, Nucleic acids research.

[102]  C. Lin,et al.  Interstitial localization of telomeric DNA sequences in the Indian muntjac chromosomes: further evidence for tandem chromosome fusions in the karyotypic evolution of the Asian muntjacs. , 1993, Cytogenetics and cell genetics.