RNA-catalysed nucleotide synthesis

  title={RNA-catalysed nucleotide synthesis},
  author={Peter J. Unrau and David P. Bartel},
The ‘RNA world’ hypothesis proposes that early life developed by making use of RNA molecules, rather than proteins, to catalyse the synthesis of important biological molecules. It is thought, however, that the nucleotides constituting RNA were scarce on early Earth. RNA-based life must therefore have acquired the ability to synthesize RNA nucleotides from simpler and more readily available precursors, such as sugars and bases. Plausible prebiotic synthesis routes have been proposed for sugars… 

RNA Synthesis by in Vitro Selected Ribozymes for Recreating an RNA World

This review focuses on three types of ribozymes that could have been involved in the synthesis of RNA, the core activity in the self-replication of RNA world organisms.

Prebiotic chemistry and the origin of the RNA world.

  • L. Orgel
  • Biology
    Critical reviews in biochemistry and molecular biology
  • 2004
The demonstration that ribosomal peptide synthesis is a ribozyme-catalyzed reaction makes it almost certain that there was once an RNA World, and a discussion of genetic systems simpler than RNA that might have "invented" RNA is discussed.

Peptidyltransfer Reaction Catalyzed by the Ribosome and the Ribozyme: a Dissertation

The newly established assay for ribosomal peptidyltransferase reaction provides a good system to investigate the mechanism of ribosome reaction and may have potential application in drug screening to search for the specific peptidoltransferase inhibitors.

DNA before proteins? Recent discoveries in nucleic acid catalysis strengthen the case.

An RNA-DNA World could arise from an all-RNA system with the development of as few as three ribozymes-a DNA-dependent RNA polymerase, an RNA-dependent DNA polymerase and a catalyst for the production of DNA nucleotides, affording the evolutionary time needed to develop protein synthesis.

A ribozyme that lacks cytidine

In vitro evolution is used to obtain an RNA ligase ribozyme that lacks cytidine and has a catalytic rate that is about 105-fold faster than the uncatalysed rate of template-directed RNA ligation.

RNA-mediated chemistries: a case of replication and capping

An RNA-capping ribozyme is isolated and characterized that retains stereochemistry during the synthesis of a 5'-5' RNA cap, and oligonucleotides are found that are able to form transient unimolccular loop structures closed by 3s little as one base-pair to be viable substrates.

Origins of Life: Emergence of the RNA World

The RNA World hypothesis refers to a period during the evolution of life on Earth, preceding the DNA/RNA/protein-based systems of modern biology, during which RNA alone directed and catalyzed the

Creation and evolution of new ribozymes.

An RNA is generated that synthesizes RNA using the same reaction as that employed by protein enzymes that catalyze RNA polymerization, and shows significant template fidelity.

RNA-Catalyzed RNA Polymerization: Accurate and General RNA-Templated Primer Extension

An RNA molecule is described that catalyzes the type of polymerization needed for RNA replication, which uses nucleoside triphosphates and the coding information of an RNA template to extend an RNA primer by the successive addition of up to 14 nucleotides.

Mechanisms of RNA catalysis

  • D. Lilley
  • Biology, Chemistry
    Philosophical Transactions of the Royal Society B: Biological Sciences
  • 2011
In the Varkud satellite ribozyme, it is shown that the cleavage reaction is catalysed by guanine and adenine nucleobases acting as general base and acid, respectively.



RNA-catalysed RNA polymerization using nucleoside triphosphates

An RNA is described that synthesizes RNA using the same reaction as that employed by protein enzymes that catalyse RNA polymerization, and shows marked template fidelity.

Rates of decomposition of ribose and other sugars: implications for chemical evolution.

The results suggest that the backbone of the first genetic material could not have contained ribose or other sugars because of their instability, and the generally accepted prebiotic synthesis of ribose, the formose reaction, yields numerous sugars without any selectivity.

Modern metabolism as a palimpsest of the RNA world.

An approach is developed for constructing models of ancient organisms using data from metabolic pathways, genetic organization, chemical structure, and enzymatic reaction mechanisms found in

A general purpose RNA-cleaving DNA enzyme.

  • S. SantoroG. F. Joyce
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
An in vitro selection procedure was used to develop a DNA enzyme that can be made to cleave almost any targeted RNA substrate under simulated physiological conditions, and its activity is dependent on the presence of Mg2+ ion.

Isolation of new ribozymes from a large pool of random sequences [see comment].

An iterative in vitro selection procedure was used to isolate a new class of catalytic RNAs (ribozymes) from a large pool of random-sequence RNA molecules, leading to improvement of the average ligation activity and the emergence of ribozymes with reaction rates 7 million times faster than the uncatalyzed reaction rate.

Dinucleoside pyrophosphate are substrates for T4-induced RNA ligase.

Despite the relative lack of specificity of RNA ligase for the P-X -group added, the failure of NADP+, deamino-NAD+, epsilonNCD+, ePSilon NAD and CoA to react indicates that the enzyme shows a high degree of selectivity for the AMP portion of the substrate.

The secondary structure and sequence optimization of an RNA ligase ribozyme.

The identification of a 112 nt ribozyme secondary structure imbedded within a 186 nt RNA is reported, indicating that when complexed with substrate RNAs the ligase forms a nested, double pseudo-knot secondary structure with seven stems and several important joining segments.

An efficient prebiotic synthesis of cytosine and uracil

In concentrated urea solution—such as might have been found in an evaporating lagoon or in pools on drying beaches on the early Earth—cyanoacetaldehyde reacts to form cytosine in yields of 30-50%, from which uracil can be formed by hydrolysis.

In vitro selection of a novel catalytic RNA: characterization of a sulfur alkylation reaction and interaction with a small peptide.

An in vitro RNA selection for catalytic activity was used to co-select for binding activity to a small peptide, showing that the intrinsic reactivity of the 5' phosphorothioate is not increased in the selected RNA.

Diversity of oligonucleotide functions.

The range of applications of this technology for new discovery extends from basic research reagents to the identification of novel diagnostic and therapeutic reagents, and examples of these applications are described.