The Dawn of the RNA World: RNA Polymerization from Monoribonucleotides under Prebiotically Plausible Conditions

2009 ◽  
pp. 88-98
Keyword(s):  
Rna World ◽  
Rna Polymerization

scholarly journals Enzymatic RNA Production from NTPs Synthesized from Nucleosides and Trimetaphosphate

2021 ◽  
Author(s):  
Fabio Chizzolini ◽  
Alexandra Kent ◽  
Luiz F. M. Passalacqua ◽  
Andrej Lupták
Keyword(s):  
Rna Synthesis ◽  
Rna World ◽  
Rna Replication ◽  
High Energy ◽  
Rna Degradation ◽  
T7 Rna Polymerase ◽  
Nucleotide Synthesis ◽  
Enthalpy Of Activation ◽  
Rna Polymerization ◽  
Synthetic Approaches

<p>A mechanism of nucleoside triphosphorylation would have been critical in an evolving “RNA world” to provide high-energy substrates for reactions such as RNA polymerization. However, synthetic approaches to produce ribonucleoside triphosphoates (rNTPs) have suffered from conditions such as high temperatures or high pH that lead to increased RNA degradation, as well as substrate production that cannot sustain replication. We demonstrate that cyclic trimetaphosphate (cTmp) can react with nucleosides to form rNTPs under mild, prebiotically-relevant conditions, with second-order rate constants ranging from 1.7 x 10<sup>–6</sup> to 6.5 x 10<sup>–6</sup> M<sup>–1</sup> s<sup>–1</sup>. The ATP reaction shows a linear dependence on pH and Mg<sup>2+</sup>, and an enthalpy of activation of 88 ± 4 kJ/mol. At millimolar nucleoside and cTmp concentrations, the rNTP production rate is sufficient to facilitate RNA synthesis by both T7 RNA polymerase and a polymerase ribozyme. We suggest that the optimized reaction of cTmp with nucleosides may provide a viable connection between prebiotic nucleotide synthesis and RNA replication.</p>

scholarly journals Enzymatic RNA Production from NTPs Synthesized from Nucleosides and Trimetaphosphate

2021 ◽  
Author(s):  
Fabio Chizzolini ◽  
Alexandra Kent ◽  
Luiz F. M. Passalacqua ◽  
Andrej Lupták
Keyword(s):  
Rna Synthesis ◽  
Rna World ◽  
Rna Replication ◽  
High Energy ◽  
Rna Degradation ◽  
T7 Rna Polymerase ◽  
Nucleotide Synthesis ◽  
Enthalpy Of Activation ◽  
Rna Polymerization ◽  
Synthetic Approaches

<p>A mechanism of nucleoside triphosphorylation would have been critical in an evolving “RNA world” to provide high-energy substrates for reactions such as RNA polymerization. However, synthetic approaches to produce ribonucleoside triphosphoates (rNTPs) have suffered from conditions such as high temperatures or high pH that lead to increased RNA degradation, as well as substrate production that cannot sustain replication. We demonstrate that cyclic trimetaphosphate (cTmp) can react with nucleosides to form rNTPs under mild, prebiotically-relevant conditions, with second-order rate constants ranging from 1.7 x 10<sup>–6</sup> to 6.5 x 10<sup>–6</sup> M<sup>–1</sup> s<sup>–1</sup>. The ATP reaction shows a linear dependence on pH and Mg<sup>2+</sup>, and an enthalpy of activation of 88 ± 4 kJ/mol. At millimolar nucleoside and cTmp concentrations, the rNTP production rate is sufficient to facilitate RNA synthesis by both T7 RNA polymerase and a polymerase ribozyme. We suggest that the optimized reaction of cTmp with nucleosides may provide a viable connection between prebiotic nucleotide synthesis and RNA replication.</p>

scholarly journals Enzymatic RNA Production from NTPs Synthesized from Nucleosides and Trimetaphosphate

2021 ◽  
Author(s):  
Fabio Chizzolini ◽  
Alexandra Kent ◽  
Luiz F. M. Passalacqua ◽  
Andrej Lupták
Keyword(s):  
Rna Synthesis ◽  
Rna World ◽  
Rna Replication ◽  
High Energy ◽  
Rna Degradation ◽  
T7 Rna Polymerase ◽  
Nucleotide Synthesis ◽  
Enthalpy Of Activation ◽  
Rna Polymerization ◽  
Synthetic Approaches

<p>A mechanism of nucleoside triphosphorylation would have been critical in an evolving “RNA world” to provide high-energy substrates for reactions such as RNA polymerization. However, synthetic approaches to produce ribonucleoside triphosphoates (rNTPs) have suffered from conditions such as high temperatures or high pH that lead to increased RNA degradation, as well as substrate production that cannot sustain replication. We demonstrate that cyclic trimetaphosphate (cTmp) can react with nucleosides to form rNTPs under mild, prebiotically-relevant conditions, with second-order rate constants ranging from 1.7 to 6.5 µM<sup>–1</sup> s<sup>–1</sup>. The ATP reaction shows a linear dependence on pH and Mg<sup>2+</sup>, and an enthalpy of activation of 88 ± 4 kJ/mol. At millimolar nucleoside and cTmp concentrations, the rNTP production rate is sufficient to facilitate RNA synthesis by both T7 RNA polymerase and a polymerase ribozyme. We suggest that the optimized reaction of cTmp with nucleosides may provide a viable connection between prebiotic nucleotide synthesis and RNA replication.<br></p>

Processive RNA polymerization and promoter recognition in an RNA World

Science ◽  
2021 ◽  
Vol 371 (6535) ◽  
pp. 1225-1232
Author(s):  
Razvan Cojocaru ◽  
Peter J. Unrau
Keyword(s):  
Rna World ◽  
Promoter Sequence ◽  
Second Step ◽  
Promoter Recognition ◽  
Rna Polymerization ◽  
Evolution Of Life ◽  
Strand Invasion ◽  
Critical Requirement ◽  
Self Replication ◽  
Rna Promoter

Early life is thought to have required the self-replication of RNA by RNA replicases. However, how such replicases evolved and subsequently enabled gene expression remains largely unexplored. We engineered and selected a holopolymerase ribozyme that uses a sigma factor–like specificity primer to first recognize an RNA promoter sequence and then, in a second step, rearrange to a processive elongation form. Using its own sequence, the polymerase can also program itself to polymerize from certain RNA promoters and not others. This selective promoter–based polymerization could allow an RNA replicase ribozyme to define “self” from “nonself,” an important development for the avoidance of replicative parasites. Moreover, the clamp-like mechanism of this polymerase could eventually enable strand invasion, a critical requirement for replication in the early evolution of life.

scholarly journals Crystal structure of an RNA polymerase ribozyme in complex with an antibody fragment

2011 ◽  
Vol 366 (1580) ◽  
pp. 2918-2928 ◽  
Author(s):  
Joseph A. Piccirilli ◽  
Yelena Koldobskaya
Keyword(s):  
Metal Ion ◽  
Rna Binding ◽  
Rna World ◽  
Three Dimensional ◽  
Antibody Fragment ◽  
Single Step ◽  
Dimensional Structure ◽  
Rna Sequences ◽  
Rna Polymerization

All models of the RNA world era invoke the presence of ribozymes that can catalyse RNA polymerization. The class I ligase ribozyme selected in vitro 15 years ago from a pool of random RNA sequences catalyses formation of a 3′,5′-phosphodiester linkage analogous to a single step of RNA polymerization. Recently, the three-dimensional structure of the ligase was solved in complex with U1A RNA-binding protein and independently in complex with an antibody fragment. The RNA adopts a tripod arrangement and appears to use a two-metal ion mechanism similar to protein polymerases. Here, we discuss structural implications for engineering a true polymerase ribozyme and describe the use of the antibody framework both as a portable chaperone for crystallization of other RNAs and as a platform for exploring steps in evolution from the RNA world to the RNA–protein world.

Randomness and Complexity

2018 ◽  
Author(s):  
Steven E. Vigdor
Keyword(s):  
Quantum Mechanics ◽  
Natural Selection ◽  
Rna World ◽  
Biological Evolution ◽  
Variable Theory ◽  
Cosmological Natural Selection ◽  
Einstein Podolsky Rosen ◽  
World Hypothesis ◽  
Rna World Hypothesis

Chapter 7 describes the fundamental role of randomness in quantum mechanics, in generating the first biomolecules, and in biological evolution. Experiments testing the Einstein–Podolsky–Rosen paradox have demonstrated, via Bell’s inequalities, that no local hidden variable theory can provide a viable alternative to quantum mechanics, with its fundamental randomness built in. Randomness presumably plays an equally important role in the chemical assembly of a wide array of polymer molecules to be sampled for their ability to store genetic information and self-replicate, fueling the sort of abiogenesis assumed in the RNA world hypothesis of life’s beginnings. Evidence for random mutations in biological evolution, microevolution of both bacteria and antibodies and macroevolution of the species, is briefly reviewed. The importance of natural selection in guiding the adaptation of species to changing environments is emphasized. A speculative role of cosmological natural selection for black-hole fecundity in the evolution of universes is discussed.

scholarly journals Are Scientific Models of Life Testable? A Lesson from Simpson’s Paradox

Sci ◽  
2020 ◽  
Vol 2 (3) ◽  
pp. 73
Author(s):  
Prasanta S. Bandyopadhyay ◽  
Nolan Grunska ◽  
Don Dcruz ◽  
Mark C. Greenwood
Keyword(s):  
Origin Of Life ◽  
Rna World ◽  
Scientific Models ◽  
Scientific Model ◽  
Simpson’S Paradox ◽  
World Theory ◽  
Life Issues ◽  
The Origin Of Life ◽  
Logical Sense ◽  
Simpson's Paradox

We address the need for a model by considering two competing theories regarding the origin of life: (i) the Metabolism First theory and (ii) the RNA World theory. We discuss two inter-related points. (I) Models are valuable tools in understanding both the processes and intricacies of the origin of life issues. (II) Insights from models also help us to evaluate the core objection to origin of life theories called “the inefficiency objection” commonly raised by proponents of both the Metabolism First theory and the RNA World theory against each other. We use Simpson’s paradox as a tool for challenging this objection. We will use models in various senses ranging from taking them as representations of reality to treating them as theories/accounts that provide heuristics for probing reality. In this paper, we will frequently use models and theories interchangeably. Additionally, we investigate Conway’s Game of Life and contrast it with our Simpson’s Paradox (SP)-based approach to emergence of life issues. Finally, we discuss some of the consequences of our view. A scientific model is testable in three senses: (i) a logical sense, (ii) a nomological sense, and (iii) a current technological sense. The SP-based model is testable in the logical sense. It is also testable nomologically. However, it is not currently feasible to test it.

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