scholarly journals Non-enzymatic primer extension with strand displacement

2019 ◽  
Author(s):  
Lijun Zhou ◽  
Seohyun Chris Kim ◽  
Katherine H. Ho ◽  
Derek K. O’Flaherty ◽  
Constantin Giurgiu ◽  
...  
Keyword(s):  
Rna World ◽  
Genetic Material ◽  
Kinetic Studies ◽  
Single Step ◽  
Primer Extension ◽  
Branch Migration ◽  
Strand Displacement ◽  
World Hypothesis ◽  
Self Replication ◽  
Rna World Hypothesis

AbstractNon-enzymatic RNA self-replication is integral to the ‘RNA World’ hypothesis. Despite considerable progress in non-enzymatic template copying, true replication remains challenging due to the difficulty of separating the strands of the product duplex. Here, we report a prebiotically plausible solution to this problem in which short ‘invader’ oligonucleotides unwind an RNA duplex through a toehold/branch migration mechanism, allowing non-enzymatic primer extension on a template that was previously occupied by its complementary strand. Kinetic studies of single-step reactions suggest that following invader binding, branch migration results in a 2:3 partition of the template between open and closed states. Finally, we demonstrate continued primer extension with strand displacement by employing activated 3′-aminonucleotides, a more reactive proxy for ribonucleotides. Our study suggests that complete cycles of non-enzymatic replication of the primordial genetic material may have been catalyzed by short RNA oligonucleotides.

scholarly journals Non-enzymatic primer extension with strand displacement

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Lijun Zhou ◽  
Seohyun Chris Kim ◽  
Katherine H Ho ◽  
Derek K O'Flaherty ◽  
Constantin Giurgiu ◽  
...  
Keyword(s):  
Rna World ◽  
Genetic Material ◽  
Kinetic Studies ◽  
Single Step ◽  
Primer Extension ◽  
Complementary Strand ◽  
Branch Migration ◽  
Strand Displacement ◽  
Migration Mechanism ◽  
Self Replication

Non-enzymatic RNA self-replication is integral to the emergence of the ‘RNA World’. Despite considerable progress in non-enzymatic template copying, demonstrating a full replication cycle remains challenging due to the difficulty of separating the strands of the product duplex. Here, we report a prebiotically plausible approach to strand displacement synthesis in which short ‘invader’ oligonucleotides unwind an RNA duplex through a toehold/branch migration mechanism, allowing non-enzymatic primer extension on a template that was previously occupied by its complementary strand. Kinetic studies of single-step reactions suggest that following invader binding, branch migration results in a 2:3 partition of the template between open and closed states. Finally, we demonstrate continued primer extension with strand displacement by employing activated 3′-aminonucleotides, a more reactive proxy for ribonucleotides. Our study suggests that complete cycles of non-enzymatic replication of the primordial genetic material may have been facilitated by short RNA oligonucleotides.

scholarly journals Origins of Life and the RNA World: Evolution of RNA-Replicase Recognition

2004 ◽  
Vol 213 ◽  
pp. 321-324 ◽  
Author(s):  
Laura Guogas ◽  
James Hogle ◽  
Lee Gehrke
Keyword(s):  
Origin Of Life ◽  
Protein Complex ◽  
Rna Viruses ◽  
Rna World ◽  
Rna Virus ◽  
Genetic Material ◽  
Virus Family ◽  
The Origin Of Life ◽  
World Hypothesis ◽  
Rna World Hypothesis

Central to understanding the origin of life is the elucidation of the first replication mechanism. The RNA World hypothesis suggests that the first self-replicating molecules were RNAs and that DNA later superceded RNA as the genetic material. RNA viruses were not subjected to the same evolutionary pressures as cellular organisms; consequently, they likely possess remnants of earlier replication strategies. Our laboratory investigates how members of the RNA virus family Bromoviridae can have structurally distinct 3' end tags yet are specifically recognized by conserved replication enzymes. This work addresses the idea that 3' tRNA tails were functionally replaced in some viruses by an RNA-protein complex. These viruses may serve as a timeline for the transition from the RNA world to DNA and protein based life.

scholarly journals Modified nucleotides may have enhanced early RNA catalysis

2020 ◽  
Vol 117 (15) ◽  
pp. 8236-8242 ◽  
Author(s):  
Steven K. Wolk ◽  
Wesley S. Mayfield ◽  
Amy D. Gelinas ◽  
David Astling ◽  
Jessica Guillot ◽  
...  
Keyword(s):  
Rna World ◽  
Rna Catalysis ◽  
Evolutionary Path ◽  
Rna Molecules ◽  
Catalytic Function ◽  
Short Rnas ◽  
World Hypothesis ◽  
First Moment ◽  
Self Replication ◽  
Rna World Hypothesis

The modern version of the RNA World Hypothesis begins with activated ribonucleotides condensing (nonenzymatically) to make RNA molecules, some of which possess (perhaps slight) catalytic activity. We propose that noncanonical ribonucleotides, which would have been inevitable under prebiotic conditions, might decrease the RNA length required to have useful catalytic function by allowing short RNAs to possess a more versatile collection of folded motifs. We argue that modified versions of the standard bases, some with features that resemble cofactors, could have facilitated that first moment in which early RNA molecules with catalytic capability began their evolutionary path toward self-replication.

scholarly journals The difficult case of an RNA-only origin of life

2019 ◽  
Vol 3 (5) ◽  
pp. 469-475 ◽  
Author(s):  
Kristian Le Vay ◽  
Hannes Mutschler
Keyword(s):  
Origin Of Life ◽  
Rna World ◽  
Large Body ◽  
Difficult Case ◽  
Experimental Approaches ◽  
World Hypothesis ◽  
Life On Earth ◽  
Self Replication ◽  
Emergence Of Life ◽  
Rna World Hypothesis

The RNA world hypothesis is probably the most extensively studied model for the emergence of life on Earth. Despite a large body of evidence supporting the idea that RNA is capable of kick-starting autocatalytic self-replication and thus initiating the emergence of life, seemingly insurmountable weaknesses in the theory have also been highlighted. These problems could be overcome by novel experimental approaches, including out-of-equilibrium environments, and the exploration of an early co-evolution of RNA and other key biomolecules such as peptides and DNA, which might be necessary to mitigate the shortcomings of RNA-only systems.

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 Transcription and translation in an RNA world

2006 ◽  
Vol 361 (1474) ◽  
pp. 1751-1760 ◽  
Author(s):  
William R Taylor
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Rna World ◽  
Large Subunit ◽  
Trna Synthetase ◽  
Nucleoside Triphosphate ◽  
Amino Acid Binding ◽  
World Hypothesis ◽  
Protein Elongation ◽  
Rna World Hypothesis

The RNA world hypothesis requires a ribozyme that was an RNA-directed RNA polymerase (ribopolymerase). If such a replicase makes a reverse complementary copy of any sequence (including itself), in a simple RNA world, there is no mechanism to prevent self-hybridization. It is proposed that this can be avoided through the synthesis of a parallel complementary copy. The logical consequences of this are pursued and developed in a computer simulation, where the behaviour of the parallel copy is compared to the conventional reverse complementary copy. It is found that the parallel copy is more efficient at higher temperatures (up to 90°C). A model for the ribopolymerase, based on the core of the large subunit (LSU) of the ribosome, is described. The geometry of a potential active site for this ribopolymerase suggests that it contained a cavity (now occupied by the aminoacyl-tRNA) and that an amino acid binding in this might have ‘poisoned’ the ribopolymerase by cross-reacting with the nucleoside-triphosphate before polymerization could occur. Based on a similarity to the active site components of the class-I tRNA synthetase enzymes, it is proposed that the amino acid could become attached to the nascent RNA transcript producing a variety of aminoacylated tRNA-like products. Using base-pairing interactions, some of these molecules might cross-link two ribopolymerases, giving rise to a precursor of the modern ribosome. A hybrid dimer, half polymerase and half proto-ribosome, could account for mRNA translocation before the advent of protein elongation factors.

scholarly journals RNA Back and Forth: Looking through Ribozyme and Viroid Motifs

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 283 ◽  
Author(s):  
Marie-Christine Maurel ◽  
Fabrice Leclerc ◽  
Jacques Vergne ◽  
Giuseppe Zaccai
Keyword(s):  
Rna World ◽  
Hammerhead Ribozyme ◽  
Intramolecular Interactions ◽  
Modern World ◽  
Widespread Occurrence ◽  
Living Fossils ◽  
Evolution Of Life ◽  
Catalytically Active ◽  
World Hypothesis ◽  
Rna World Hypothesis

Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the “RNA world” hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the widespread occurrence of HHRs in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitous features of life. Those are the structural and functional versatility of small RNAs, ribozymes, and viroids, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.

The “Strong” RNA World Hypothesis: Fifty Years Old

Astrobiology ◽  
2013 ◽  
Vol 13 (4) ◽  
pp. 391-403 ◽  
Author(s):  
Marc Neveu ◽  
Hyo-Joong Kim ◽  
Steven A. Benner
Keyword(s):  
Rna World ◽  
World Hypothesis ◽  
Rna World Hypothesis

scholarly journals Solvent viscosity facilitates replication and ribozyme catalysis from an RNA duplex in a model prebiotic process

2019 ◽  
Vol 47 (13) ◽  
pp. 6569-6577 ◽  
Author(s):  
Christine He ◽  
Adriana Lozoya-Colinas ◽  
Isaac Gállego ◽  
Martha A Grover ◽  
Nicholas V Hud
Keyword(s):  
Information Transfer ◽  
Rna World ◽  
Hammerhead Ribozyme ◽  
Information Storage ◽  
Additional Challenge ◽  
The Origin Of Life ◽  
World Hypothesis ◽  
Synthesis Reactions ◽  
Rna World Hypothesis ◽  
Single Sequence

Abstract The RNA World hypothesis posits that RNA was once responsible for genetic information storage and catalysis. However, a prebiotic mechanism has yet to be reported for the replication of duplex RNA that could have operated before the emergence of polymerase ribozymes. Previously, we showed that a viscous solvent enables information transfer from one strand of long RNA duplex templates, overcoming ‘the strand inhibition problem'. Here, we demonstrate that the same approach allows simultaneous information transfer from both strands of long duplex templates. An additional challenge for the RNA World is that structured RNAs (like those with catalytic activity) function poorly as templates in model prebiotic RNA synthesis reactions, raising the question of how a single sequence could serve as both a catalyst and as a replication template. Here, we show that a viscous solvent also facilitates the transition of a newly synthesized hammerhead ribozyme sequence from its inactive, duplex state to its active, folded state. These results demonstrate how fluctuating environmental conditions can allow a ribozyme sequence to alternate between acting as a template for replication and functioning as a catalyst, and illustrate the potential for temporally changing environments to enable molecular processes necessary for the origin of life.

scholarly journals Expanding the informational chemistries of life: peptide/RNA networks

2017 ◽  
Vol 375 (2109) ◽  
pp. 20160356 ◽  
Author(s):  
Olga Taran ◽  
Chenrui Chen ◽  
Tolulope O. Omosun ◽  
Ming-Chien Hsieh ◽  
Allisandra Rha ◽  
...  
Keyword(s):  
Rna World ◽  
Chemical Information ◽  
Disease States ◽  
Complementary Approach ◽  
The Subject ◽  
Active Research ◽  
World Hypothesis ◽  
Reaction Cascades ◽  
Rna World Hypothesis ◽  
Emergent Behaviours

The RNA world hypothesis simplifies the complex biopolymer networks underlining the informational and metabolic needs of living systems to a single biopolymer scaffold. This simplification requires abiotic reaction cascades for the construction of RNA, and this chemistry remains the subject of active research. Here, we explore a complementary approach involving the design of dynamic peptide networks capable of amplifying encoded chemical information and setting the stage for mutualistic associations with RNA. Peptide conformational networks are known to be capable of evolution in disease states and of co-opting metal ions, aromatic heterocycles and lipids to extend their emergent behaviours. The coexistence and association of dynamic peptide and RNA networks appear to have driven the emergence of higher-order informational systems in biology that are not available to either scaffold independently, and such mutualistic interdependence poses critical questions regarding the search for life across our Solar System and beyond. This article is part of the themed issue ‘Reconceptualizing the origins of life’.

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