The eightfold path to non-enzymatic RNA replication

The first RNA World models were based on the concept of an RNA replicase - a ribozyme that was a good enough RNA polymerase that it could catalyze its own replication. Although several RNA polymerase ribozymes have been evolved in vitro, the creation of a true replicase remains a great experimental challenge. At first glance the alternative, in which RNA replication is driven purely by chemical and physical processes, seems even more challenging, given that so many unsolved problems appear to stand in the way of repeated cycles of non-enzymatic RNA replication. Nevertheless the idea of non-enzymatic RNA replication is attractive, because it implies that the first heritable functional RNA need not have improved replication, but could have been a metabolic ribozyme or structural RNA that conferred any function that enhanced protocell reproduction or survival. In this review, I discuss recent findings that suggest that chemically driven RNA replication may not be completely impossible.

[1]  J. Szostak,et al.  Evolution of functional nucleic acids in the presence of nonheritable backbone heterogeneity , 2011, Proceedings of the National Academy of Sciences.

[2]  J. Szostak,et al.  Thermostability of model protocell membranes , 2008, Proceedings of the National Academy of Sciences.

[3]  P. Cramer,et al.  Structural Basis of Transcription: RNA Polymerase II at 2.8 Ångstrom Resolution , 2001, Science.

[4]  L. Orgel,et al.  Molecular replication , 1992, Nature.

[5]  A. J. Bennet,et al.  A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites. , 1999, Chemistry & biology.

[6]  G. Eichhorn,et al.  Interaction of metal ions with nucleic acids and related compounds. XVII. On the mechanism of degradation of polyribonucleotides and oligoribonucleotides by zinc(II) ions. , 1971, Biochemistry.

[7]  J. Szostak,et al.  Coupled Growth and Division of Model Protocell Membranes , 2009, Journal of the American Chemical Society.

[8]  E. Szathmáry,et al.  In silico simulations reveal that replicators with limited dispersal evolve towards higher efficiency and fidelity , 2002, Nature.

[9]  Gerald F. Joyce,et al.  1 Prospects for Understanding the Origin of the RNA World , 1993 .

[10]  L. Shrestha,et al.  Aqueous Phase Behavior of Diglycerol Fatty Acid Esters , 2007 .

[11]  J. Szostak,et al.  Mutant ATP-binding RNA aptamers reveal the structural basis for ligand binding. , 1997, Journal of molecular biology.

[12]  D. Bartel,et al.  Synthesizing life , 2001, Nature.

[13]  N. Arnheim,et al.  Extension of base mispairs by Taq DNA polymerase: implications for single nucleotide discrimination in PCR. , 1992, Nucleic acids research.

[14]  Wen Zhang,et al.  High fidelity of base pairing by 2-selenothymidine in DNA. , 2010, Journal of the American Chemical Society.

[15]  L. Orgel,et al.  Synthesis of long prebiotic oligomers on mineral surfaces , 1996, Nature.

[16]  P. Holliger,et al.  Ribozyme-Catalyzed Transcription of an Active Ribozyme , 2011, Science.

[17]  G. F. Joyce.  RNA evolution and the origins of life , 1989, Nature.

[18]  L. Orgel,et al.  Prebiotic chemistry and the origin of the RNA world. , 2004, Critical reviews in biochemistry and molecular biology.

[19]  K. Severinov,et al.  Crystal Structure of Thermus aquaticus Core RNA Polymerase at 3.3 Å Resolution , 1999, Cell.

[20]  C. Richert,et al.  Accelerating chemical replication steps of RNA involving activated ribonucleotides and downstream-binding elements. , 2005, Chemical communications.

[21]  L. Orgel,et al.  Amino acid dependent formation of phosphate anhydrides in water mediated by carbonyl sulfide. , 2006, Journal of the American Chemical Society.

[22]  J. Cherayil,et al.  Thionucleosides in transfer ribonucleic acid: diversity, structure, biosynthesis, and function. , 1988, Microbiological reviews.

[23]  R. Rosenfeld.  Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[24]  Eörs Szathmáry,et al.  Real ribozymes suggest a relaxed error threshold , 2005, Nature Genetics.

[25]  A. Woody,et al.  Asp537 and Asp812 in bacteriophage T7 RNA polymerase as metal ion-binding sites studied by EPR, flow-dialysis, and transcription. , 1996, Biochemistry.

[26]  C. Richert,et al.  Adenosine residues in the template do not block spontaneous replication steps of RNA. , 2007, Chemical communications.

[27]  L. Orgel,et al.  Oligomerization of (guanosine 5'-phosphor)-2-methylimidazolide on poly(C). An RNA polymerase model. , 1982, Journal of molecular biology.

[28]  J. Sutherland,et al.  Prebiotic chemistry: a new modus operandi , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[29]  G. Wahl,et al.  Derivatization of unprotected polynucleotides. , 1983, Nucleic acids research.

[30]  Xiaoyu Li,et al.  DNA-catalyzed polymerization. , 2002, Journal of the American Chemical Society.

[31]  J. Szostak,et al.  Origin of life on earth. , 2009, Scientific American.

[32]  A. Noronha,et al.  Physicochemical and biochemical properties of 2',5'-linked RNA and 2',5'-RNA:3',5'-RNA "hybrid" duplexes. , 1998, Biochemistry.

[33]  J. Steitz,et al.  A general two-metal-ion mechanism for catalytic RNA. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Larry W. McLaughlin,et al.  High fidelity TNA synthesis by Therminator polymerase , 2005, Nucleic acids research.

[35]  R. Kierzek,et al.  Role of unsatisfied hydrogen bond acceptors in RNA energetics and specificity. , 2010, Journal of the American Chemical Society.

[36]  Gerald F. Joyce,et al.  2 Prospects for Understanding the Origin of the RNA World , 1999 .

[37]  N. Hud,et al.  Intercalation as a means to suppress cyclization and promote polymerization of base-pairing oligonucleotides in a prebiotic world , 2010, Proceedings of the National Academy of Sciences.

[38]  D. Turner,et al.  Thermodynamics of RNA-RNA duplexes with 2- or 4-thiouridines: implications for antisense design and targeting a group I intron. , 1999, Biochemistry.

[39]  J. Sutherland,et al.  Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions , 2009, Nature.

[40]  A. Ferré-D’Amaré,et al.  Small self-cleaving ribozymes. , 2010, Cold Spring Harbor perspectives in biology.

[41]  A D Ellington,et al.  Surprising fidelity of template-directed chemical ligation of oligonucleotides. , 1997, Chemistry & biology.

[42]  W. Gilbert.  Origin of life: The RNA world , 1986, Nature.

[43]  Martin A. Nowak,et al.  Effect of Stalling after Mismatches on the Error Catastrophe in Nonenzymatic Nucleic Acid Replication , 2010, Journal of the American Chemical Society.

[44]  J. Szostak,et al.  Template-directed synthesis of a genetic polymer in a model protocell , 2008, Nature.

[45]  Irene A. Chen,et al.  The prebiotic evolutionary advantage of transferring genetic information from RNA to DNA , 2011, Nucleic acids research.

[46]  T. Steitz,et al.  Crystal structures of an NH2-terminal fragment of T4 DNA polymerase and its complexes with single-stranded DNA and with divalent metal ions. , 1996, Biochemistry.

[47]  P. Gilham.  An Addition Reaction Specific for Uridine and Guanosine Nucleotides and its Application to the Modification of Ribonuclease Action , 1962 .

[48]  D. Bartel,et al.  Synthesizing life : Paths to unforeseeable science & technology , 2001 .

[49]  P. A. Giannaris,et al.  Oligoribonucleotides containing 2',5'-phosphodiester linkages exhibit binding selectivity for 3',5'-RNA over 3',5'-ssDNA. , 1993, Nucleic acids research.

[50]  L E Orgel,et al.  Non-enzymatic transcription of an oligodeoxynucleotide 14 residues long. , 1987, Journal of molecular biology.

[51]  Zhen Huang,et al.  Biochemistry of Selenium‐Derivatized Naturally Occurring and Unnatural Nucleic Acids , 2008, Chemistry & biodiversity.

[52]  Andres F. Hernandez,et al.  STEP-GROWTH CONTROL IN TEMPLATE-DIRECTED POLYMERIZATION** , 2010 .

[53]  D. Turner,et al.  Improved free-energy parameters for predictions of RNA duplex stability. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[54]  L. Orgel,et al.  Carbonyl Sulfide-Mediated Prebiotic Formation of Peptides , 2004, Science.

[55]  Hani S. Zaher,et al.  Selection of an improved RNA polymerase ribozyme with superior extension and fidelity. , 2007, RNA.

[56]  R. E. Sweeney,et al.  Exploration and discovery in Yellowstone Lake: Results from high-resolution sonar imaging, seismic reflection profiling, and submersible studies , 2003 .

[57]  D. Turner,et al.  Association of 2'-5' oligoribonucleotides. , 1992, Nucleic acids research.

[58]  Jack W. Szostak,et al.  An optimal degree of physical and chemical heterogeneity for the origin of life? , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[59]  D P Glavin,et al.  Amino acids in the Martian meteorite Nakhla. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[60]  T. Steitz,et al.  Structural and functional insights provided by crystal structures of DNA polymerases and their substrate complexes. , 1998, Current opinion in structural biology.

[61]  J W Szostak,et al.  RNA aptamers that bind flavin and nicotinamide redox cofactors. , 1995, Journal of the American Chemical Society.

[62]  L. Orgel,et al.  Catalysis of accurate poly(C)-directed synthesis of 3'-5'-linked oligoguanylates by Zn2+. , 1980, Journal of molecular biology.

[63]  J. Szostak,et al.  Physical effects underlying the transition from primitive to modern cell membranes , 2011, Proceedings of the National Academy of Sciences.

[64]  R. Pascal,et al.  Amino acid N-carboxyanhydrides: activated peptide monomers behaving as phosphate-activating agents in aqueous solution. , 2004, Journal of the American Chemical Society.

[65]  A W Schwartz,et al.  The case for an ancestral genetic system involving simple analogues of the nucleotides. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[66]  B. Diop-Frimpong,et al.  Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2′-O-[2-(methoxy)ethyl]-2-thiothymidines , 2005, Nucleic acids research.

[67]  Clemens Richert,et al.  Efficient enzyme-free copying of all four nucleobases templated by immobilized RNA. , 2011, Nature chemistry.

[68]  M. Eigen.  Selforganization of matter and the evolution of biological macromolecules , 1971, Naturwissenschaften.

[69]  B. Ganem.  RNA world , 1987, Nature.

[70]  J. Szostak,et al.  Efficient and Rapid Template-Directed Nucleic Acid Copying Using 2′-Amino-2′,3′-dideoxyribonucleoside−5′-Phosphorimidazolide Monomers , 2009, Journal of the American Chemical Society.

[71]  J W Szostak,et al.  Nonenzymatic, template-directed ligation of oligoribonucleotides is highly regioselective for the formation of 3'-5' phosphodiester bonds. , 1996, Journal of the American Chemical Society.

[72]  S. Miller,et al.  Which organic compounds could have occurred on the prebiotic earth? , 1987, Cold Spring Harbor Symposia on Quantitative Biology.