RNA world - Knowledge

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metabolism, with two basic choices: non-covalent binding or covalent attachment. Both approaches have been demonstrated using directed evolution to reinvent RNA dupes of protein-catalyzed processes. Lorsch and Szostak investigated ribozymes that could phosphorylate themselves and use ATP-γS as a substrate. However, only one of the seven classes of selected ribozymes had detectable ATP affinity, indicating that the ability to bind ATP was compromised. NAD- dependent redox ribozymes were also evaluated. The select ribozyme had a rate of enhancement of more than 10 fold and was proven to catalyze the reverse reaction - benzaldehyde reduction by NADH. Since the usage of adenosine as a cofactor is prevalent in current metabolism and is likely to have been common in the RNA world, these discoveries are essential for the evolution of metabolism in the RNA world.

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fuse with another haploid protocell to form a transient diploid. The retention of the haploid state maximizes the growth rate. The periodic fusions permit mutual reactivation of otherwise lethally damaged protocells. If at least one damage-free copy of each RNA gene is present in the transient diploid, viable progeny can be formed. For two, rather than one, viable daughter cells to be produced would require an extra replication of the intact RNA gene homologous to any RNA gene that had been damaged prior to the division of the fused protocell. The cycle of haploid reproduction, with occasional fusion to a transient diploid state, followed by splitting to the haploid state, can be considered to be the sexual cycle in its most primitive form. In the absence of this sexual cycle, haploid protocells with damage in an essential RNA gene would simply die.

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the Peptide-RNA world, and offers a possible explanation for the rapid evolution of high-quality replication in RNA (since proteins are catalysts), with the disadvantage of having to postulate the coincident formation of two complex molecules, an enzyme (from peptides) and a RNA (from nucleotides). In this Peptide-RNA World scenario, RNA would have contained the instructions for life, while peptides (simple protein enzymes) would have accelerated key chemical reactions to carry out those instructions. The study leaves open the question of exactly how those primitive systems managed to replicate themselves — something neither the RNA World hypothesis nor the Peptide-RNA World theory can yet explain, unless

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lake in Lassen Volcanic National Park, California, they uncovered evidence that a simple DNA virus had acquired a gene from a completely unrelated RNA-based virus. Virologist Luis Villareal of the University of California Irvine also suggests that viruses capable of converting an RNA-based gene into DNA and then incorporating it into a more complex DNA-based genome might have been common in the virus world during the RNA to DNA transition some 4 billion years ago. This finding bolsters the argument for the transfer of information from the RNA world to the emerging DNA world before the emergence of the

1053:, whose genome consists of 8 physically separated single-stranded RNA segments, is an example of this type of virus. In segmented RNA viruses, "mating" can occur when a host cell is infected by at least two virus particles. If these viruses each contain an RNA segment with a lethal damage, multiple infection can lead to reactivation providing that at least one undamaged copy of each virus gene is present in the infected cell. This phenomenon is known as "multiplicity reactivation". Multiplicity reactivation has been reported to occur in influenza virus infections after induction of RNA damage by 7784: 461: 770:

nucleobase elaboration, to 2',3'-cyclic pyrimidine nucleotides directly, which are known to be able to polymerise into RNA. Organic chemist Donna Blackmond described this finding as "strong evidence" in favour of the RNA world. However, John Sutherland said that while his team's work suggests that nucleic acids played an early and central role in the origin of life, it did not necessarily support the RNA world hypothesis in the strict sense, which he described as a "restrictive, hypothetical arrangement".

866:), there existed free-floating nucleotides. These nucleotides regularly formed bonds with one another, which often broke because the change in energy was so low. However, certain sequences of base pairs have catalytic properties that lower the energy of their chain being created, enabling them to stay together for longer periods of time. As each chain grew longer, it attracted more matching nucleotides faster, causing chains to now form faster than they were breaking down. 38: 1042:

organism, the proportion of available resources tied up in the genetic material would be a large fraction of the total resource budget. Under limited resource conditions, the protocell reproductive rate would likely be inversely related to ploidy number. The protocell's fitness would be reduced by the costs of redundancy. Consequently, coping with damaged RNA genes while minimizing the costs of redundancy would likely have been a fundamental problem for early protocells.

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proposed a scenario whereby the critical electrochemistry of enzymatic reactions would have necessitated retention of the specific nucleotide moieties of the original RNA-based enzymes carrying out the reactions, while the remaining structural elements of the enzymes were gradually replaced by protein, until all that remained of the original RNAs were these nucleotide cofactors, "fossils of nucleic acid enzymes". The phrase "RNA World" was first used by Nobel laureate

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ribozyme was engineered to remain linked to its new, synthesized RNA strand; this allowed the team to isolate successful polymerases. The isolated RNA polymerases were again used for another round of evolution. After several rounds of evolution, they obtained one RNA polymerase ribozyme called 24-3 that was able to copy almost any other RNA, from small catalysts to long RNA-based enzymes. Particular RNAs were amplified up to 10,000 times, a first RNA version of the

372:, also called DNAzyme) with RNA-cleavage activity. After only a few weeks, a DNAzyme with significant catalytic activity had evolved. In general, DNA is much more chemically inert than RNA and hence much more resistant to obtaining catalytic properties. If in vitro evolution works for DNA it will happen much more easily with RNA. In 2022, Nick Lane and coauthors showed in a computational simulation that short RNA sequences could have been capable of catalyzing CO 7766: 8977: 833:

compounds. Aspartic acid could have been available from prebiotic synthesis or from the ribozyme synthesis of pyrimidines." This supports that NAD could have originated in the RNA world. RNA sequences at lengths of 30 nucleotides, 60 nucleotides, 100 nucleotides, and 140 nucleotides, were capable of catalysis of "the synthesis of three common coenzymes, CoA, NAD, and FAD, from their precursors, 4‘-phosphopantetheine, NMN, and FMN, respectively".

842: 7775: 990:, the first representatives of a novel domain of "subviral pathogens". Viroids infect plants, where most are pathogens, and consist of short stretches of highly complementary, circular, single-stranded and non-coding RNA without a protein coat. They are extremely small, ranging from 246 to 467 nucleobases, compared to the smallest known viruses capable of causing an infection, with genomes about 2,000 nucleobases in length. 1015:, did not evolve until billions of years after the RNA world was replaced, making viroids more likely to have arisen through later evolutionary mechanisms unrelated to the RNA world than to have survived via a cryptic host over that extended period. Whether they are relics of that world or of more recent origin, their function as autonomous naked RNA is seen as analogous to that envisioned for an RNA world. 9001: 8989: 457:). The overall structure of RNA and DNA are immensely similar—one strand of DNA and one of RNA can bind to form a double helical structure. This makes the storage of information in RNA possible in a very similar way to the storage of information in DNA. However, RNA is less stable, being more prone to hydrolysis due to the presence of a hydroxyl group at the ribose 2' position. 616:. Riboswitch classes have highly conserved aptamer domains, even among diverse organisms. When a target metabolite is bound to this aptamer, conformational changes occur, modulating the expression of genes carried by mRNA. These changes occur in an expression platform, located downstream from the aptamer. This change in structure can result in the formation or disruption of a 338:

error rate of just 1.1% per nucleotide when synthesizing an 11-nucleotide long RNA strand from primed template strands. This 189-base pair ribozyme could polymerize a template of at most 14 nucleotides in length, which is too short for self-replication, but is a potential lead for further investigation. The longest

829:, key molecular precursors of the RNA World scenario, are among the most abundant chemical families in the universe and have been found in molecular clouds in the center of the Milky Way, protostars of different masses, meteorites and comets, and also in the atmosphere of Titan, the largest moon of Saturn. 773:

The Sutherland group's 2009 paper also highlighted the possibility for the photo-sanitization of the pyrimidine-2',3'-cyclic phosphates. A potential weakness of these routes is the generation of enantioenriched glyceraldehyde, or its 3-phosphate derivative (glyceraldehyde prefers to exist as its keto

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RNA is thought to have preceded DNA, because of their ordering in the biosynthetic pathways. The deoxyribonucleotides used to make DNA are made from ribonucleotides, the building blocks of RNA, by removing the 2'-hydroxyl group. As a consequence, a cell must have the ability to make RNA before it can

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simple chemical reactions—which would enhance creation of molecules that are building blocks of RNA molecules (i.e., a strand of RNA that would make creating more strands of RNA easier). Relatively short RNA molecules with such abilities have been artificially formed in the lab. A recent study showed

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The characteristics of viroids highlighted as consistent with an RNA world were their small size, high guanine and cytosine content, circular structure, structural periodicity, the lack of protein-coding ability and, in some cases, ribozyme-mediated replication. One aspect critics of the hypothesis

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allows for inversion about the 1' anomeric centre to give the correct beta stereochemistry; one problem with this chemistry is the selective phosphorylation of alpha-cytidine at the 2' position. However, in 2009, they showed that the same simple building blocks allow access, via phosphate controlled

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ribose aminooxazoline if the enantiomeric excess of glyceraldehyde is 60% or greater, of possible interest toward biological homochirality. This can be viewed as a prebiotic purification step, where the said compound spontaneously crystallised out from a mixture of the other pentose aminooxazolines.

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coined the term in 1986. Alternative chemical paths to life have been proposed, and RNA-based life may not have been the first life to exist. Even so, the RNA world hypothesis seems to be the most favored abiogenesis paradigm, but even proponents agree it still has not reached conclusive evidence to

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Nucleotides are the fundamental molecules that combine in series to form RNA. They consist of a nitrogenous base attached to a sugar-phosphate backbone. RNA is made of long stretches of specific nucleotides arranged so that their sequence of bases carries information. The RNA world hypothesis holds

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Protein enzymes catalyze various chemical reactions, but over half of them incorporate cofactors to facilitate and diversify their catalytic activities. Cofactors are essential in biology, as they are based largely on nucleotides rather than amino acids. Ribozymes use nucleotide cofactors to create

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activity, fully able to catalyze the formation of peptide bonds between amino acids. A pseudo 2 fold symmetry of the region surrounding the peptidyl transferase center led to the hypothesis of the Proto-Ribosome, that a vestige of an ancient dimeric molecule from the RNA world is functioning within

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performed by a ribozyme polymerase was 20 bases. In 2016, researchers reported the use of in vitro evolution to improve dramatically the activity and generality of an RNA polymerase ribozyme by selecting variants that can synthesize functional RNA molecules from an RNA template. Each RNA polymerase

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in 1972 laid out a possible process by which the modern genetic system might have arisen from a nucleotide-based precursor, and this led Harold White in 1976 to observe that many of the cofactors essential for enzymatic function are either nucleotides or could have been derived from nucleotides. He

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Another proposal is that the dual-molecule system we see today, where a nucleotide-based molecule is needed to synthesize protein, and a peptide-based (protein) molecule is needed to make nucleic acid polymers, represents the original form of life. This theory is called RNA-peptide coevolution, or

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A cost-benefit analysis was carried out in which the costs of maintaining redundancy were balanced against the costs of genome damage. This analysis led to the conclusion that, under a wide range of circumstances, the selected strategy would be for each protocell to be haploid, but to periodically

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were composed of single-stranded RNA, and that individual genes corresponded to separate RNA segments, rather than being linked end-to-end as in present-day DNA genomes. A protocell that was haploid (one copy of each RNA gene) would be vulnerable to damage, since a single lesion in any RNA segment

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One of the challenges posed by the RNA world hypothesis is to discover the pathway by which an RNA-based system transitioned to one based on DNA. Geoffrey Diemer and Ken Stedman, at Portland State University in Oregon, may have found a solution. While conducting a survey of viruses in a hot acidic

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The properties of RNA make the idea of the RNA world hypothesis conceptually plausible, though its general acceptance as an explanation for the origin of life requires further evidence. RNA is known to form efficient catalysts and its similarity to DNA makes clear its ability to store information.

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The RNA world hypothesis places RNA at center-stage when life originated. The RNA world hypothesis is supported by the observations that ribosomes are ribozymes: the catalytic site is composed of RNA, and proteins hold no major structural role and are of peripheral functional importance. This was

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Vulnerability to damage could be reduced by maintaining two or more copies of each RNA segment in each protocell, i.e., by maintaining diploidy or polyploidy. Genome redundancy would allow a damaged RNA segment to be replaced by an additional replication of its homolog. However, for such a simple

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The relative chemical complexity of the nucleotide and the unlikelihood of it spontaneously arising, along with the limited number of combinations possible among four base forms, as well as the need for RNA polymers of some length before seeing enzymatic activity, have led some to reject the RNA

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A study in 2001 shows that nicotinic acid and its precursor, quinolinic acid can be "produced in yields as high as 7% in a six-step nonenzymatic sequence from aspartic acid and dihydroxyacetone phosphate (DHAP). The biosynthesis of ribose phosphate could have produced DHAP and other three carbon

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or synthesize other RNA molecules; relatively short RNA molecules that can synthesize others have been artificially produced in the lab. The shortest was 165 bases long, though it has been estimated that only part of the molecule was crucial for this function. One version, 189 bases long, had an

425:, and it has been suggested that rRNA has evolved from a similar molecule. It has also been suggested that amino acids may have initially been involved with RNA molecules as cofactors enhancing or diversifying their enzymatic capabilities, before evolving into more complex peptides. Similarly, 421:

the ribosome. An RNA molecule with the ribosomal RNA sequence has been synthesized in the lab to test the Proto-ribosome hypothesis and was able to dimerize and to form peptide bonds. A much shorter RNA molecule has been synthesized in the laboratory with the ability to form

825:, which is located 400 light years from Earth. Because glycolaldehyde is needed to form RNA, this finding suggests that complex organic molecules may form in stellar systems prior to the formation of planets, eventually arriving on young planets early in their formation. 958:

with them but may have been discarded by evolution in exchange for more optimal base pairs. Specifically, TAP can form nucleotides with a large range of sugars. Both TAP and melamine base pair with barbituric acid. All three spontaneously form nucleotides with ribose.

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Pyrimidine ribonucleosides and their respective nucleotides have been prebiotically synthesised by a sequence of reactions that by-pass free sugars and assemble in a stepwise fashion by including nitrogenous and oxygenous chemistries. In a series of publications,

546:, and its production requires less energy. In terms of base pairing, this has no effect. Adenine readily binds uracil or thymine. Uracil is, however, one product of damage to cytosine that makes RNA particularly susceptible to mutations that can replace a 869:

These chains have been proposed by some as the first, primitive forms of life. In an RNA world, different sets of RNA strands would have had different replication outputs, which would have increased or decreased their frequency in the population, i.e.,

1251:, in streams of water irradiated by UV light, could produce the chemical components of proteins and lipids, alongside those of RNA. The researchers used the term "cyanosulfidic" to describe this network of reactions. In November 2017, a team at the 644:

does, and to perform enzymatic reactions, like protein-based enzymes. Because it can carry out the types of tasks now performed by proteins and DNA, RNA is believed to have once been capable of supporting independent life on its own. Some

1283:'s elucidation of DNA structure in 1953, life was largely defined in terms of DNA and proteins: DNA and proteins seemed the dominant macromolecules in the living cell, with RNA only aiding in creating proteins from the DNA blueprint. 589:

system impossible, simply energy intensive (to repair or replace damaged RNA molecules) and prone to mutation. While this makes it unsuitable for current 'DNA optimised' life, it may have been acceptable for more primitive life.

199:). This suggests that life could not have arisen in its current form, which has led researchers to hypothesize mechanisms whereby the current system might have arisen from a simpler precursor system. American molecular biologist 3977:

Patton, John T. Editor (2008). Segmented Double-stranded RNA Viruses: Structure and Molecular Biology. Caister Academic Press. Editor's affiliation: Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD 20892-8026.

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Rivilla, Víctor M.; Jiménez-Serra, Izaskun; Martín-Pintado, Jesús; Colzi, Laura; Tercero, Belén; de Vicente, Pablo; Zeng, Shaoshan; Martín, Sergio; García de la Concepción, Juan; Bizzocchi, Luca; Melosso, Mattia (2022).

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The hypothesized existence of an RNA world does not exclude a "Pre-RNA world", where a metabolic system based on a different nucleic acid is proposed to pre-date RNA. A candidate nucleic acid is peptide nucleic acid

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Fialho DM, Clarke KC, Moore MK, Schuster GB, Krishnamurthy R, Hud NV (February 2018). "Glycosylation of a model proto-RNA nucleobase with non-ribose sugars: implications for the prebiotic synthesis of nucleosides".

281:(GNA). Despite their structural simplicity and possession of properties comparable with RNA, the chemically plausible generation of "simpler" nucleic acids under prebiotic conditions has yet to be demonstrated. 244:

Opinions differ, however, as to whether RNA constituted the first autonomous self-replicating system or was a derivative of a still-earlier system. One version of the hypothesis is that a different type of

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was RNA-based and evolved RNA viruses. Some of the viruses evolved into DNA viruses to protect their genes from attack. Through the process of viral infection into hosts the three domains of life evolved.

874:. As the fittest sets of RNA molecules expanded their numbers, novel catalytic properties added by mutation, which benefitted their persistence and expansion, could accumulate in the population. Such an 6267:

Bernstein MP, Sandford SA, Allamandola LJ, Gillette JS, Clemett SJ, Zare RN (February 1999). "UV irradiation of polycyclic aromatic hydrocarbons in ices: production of alcohols, quinones, and ethers".

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Egholm M, Buchardt O, Christensen L, Behrens C, Freier SM, Driver DA, et al. (October 1993). "PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules".

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seen in life's nucleic acids. The nucleoside cytosine has a half-life in isolation of 19 days at 100 °C (212 °F) and 17,000 years in freezing water, which some argue is too short on the

900:). These amino acids could then assist with RNA synthesis, giving those RNA chains that could serve as ribozymes the selective advantage. The ability to catalyze one step in protein synthesis, 1978: 1225:

world hypothesis in favor of a metabolism-first hypothesis, where the chemistry underlying cellular function arose first, along with the ability to replicate and facilitate this metabolism.

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was the first to posit a coherent hypothesis on the origin of nucleotides as precursors of life. In an article he contributed to a volume issued in honor of Nobel-laureate physiologist

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This model for the early sexual cycle is hypothetical, but it is very similar to the known sexual behavior of the segmented RNA viruses, which are among the simplest organisms known.

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Aminooxazolines can react with cyanoacetylene in a mild and highly efficient manner, controlled by inorganic phosphate, to give the cytidine ribonucleotides. Photoanomerization with

1650: 207:, he explained that the primitive Earth's environment could have produced RNA molecules (polynucleotide monomers) that eventually acquired enzymatic and self-replicating functions. 91:

completely falsify other paradigms and hypotheses. The concurrent formation of all four RNA building blocks further strengthened the hypothesis. Regardless of its plausibility in a

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Powner MW, Sutherland JD (October 2008). "Potentially prebiotic synthesis of pyrimidine beta-D-ribonucleotides by photoanomerization/hydrolysis of alpha-D-cytidine-2'-phosphate".

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sugar in RNA (illustration, right). This group makes the molecule less stable because, when not constrained in a double helix, the 2' hydroxyl can chemically attack the adjacent

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In the 1980s, RNA structures capable of self-processing were discovered, with the RNA moiety of RNase P acting as its catalytic subunit. These catalytic RNAs were referred to as

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and other backbone sugars could be stable enough to be found in the original genetic material, and have raised the issue that all ribose molecules would have had to be the same

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and other RNAs considered candidates at the time. Diener's hypothesis would be expanded by the research group of Ricardo Flores, and gained a broader audience when in 2014, a

1221:. Panspermia does not invalidate the concept of an RNA world, but posits that this world or its precursors originated not on Earth but rather another, probably older, planet. 358:

that almost any nucleic acid can evolve into a catalytic sequence under appropriate selection. For instance, an arbitrarily chosen 50-nucleotide DNA fragment encoding for the

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RNAs are known to play roles in other cellular catalytic processes, specifically in the targeting of enzymes to specific RNA sequences. In eukaryotes, the processing of

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RNA is a very similar molecule to DNA, with only two significant chemical differences (the backbone of RNA uses ribose instead of deoxyribose and its nucleobases include

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has been working on a novel hypothesis, called "three viruses, three domains": that viruses were instrumental in the transition from RNA to DNA and the evolution of

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suggested that a RNA world may have emerged in warm ponds on the early Earth, and that meteorites were a plausible and probable source of the RNA building blocks (

1838: 159:), which in turn ushered in the era of DNA and longer proteins. DNA has greater stability and durability than RNA; this may explain why it became the predominant 8628: 7956: 7897: 7805: 6195: 2784:

Johnston WK, Unrau PJ, Lawrence MS, Glasner ME, Bartel DP (May 2001). "RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension".

1205:. It discusses the possibility that the earliest life on this planet was carried here from somewhere else in the galaxy, possibly on meteorites similar to the 8717: 8533: 8468: 8408: 8336: 8242: 8136: 8006: 7961: 7632: 8797: 4631: 1145:

to link nucleobases. PNA is more stable than RNA, but its ability to be generated under prebiological conditions has yet to be demonstrated experimentally.

8262: 8106: 8076: 2767: 689:, which could serve just as well but are practically never used except as building blocks for nucleic acid chains. Experiments with basic ribozymes, like 175:

contain both nucleotide and amino-acid characteristics, it may be that amino acids, peptides and finally proteins initially were cofactors for ribozymes.

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RNA, have shown that simple self-replicating RNA structures can withstand even strong selective pressures (e.g., opposite-chirality chain terminators).

254:, was the first one to emerge as a self-reproducing molecule, to be replaced by RNA only later. On the other hand, the discovery in 2009 that activated 8217: 3448:"The Pyridine Nucleotide Coenzymes. Herausgegeben von J. Everse, B. Anderson und K.-S. You. Academic Press, New York 1982. XXXV, 389 S., geb. $ 46.00" 954:(TAP). These three molecules are simpler versions of the four bases in current RNA, which could have been present in larger amounts and could still be 1966: 1198:

proposes that simple metabolic processes developed before genetic materials did, and these energy-producing cycles catalyzed the production of genes.

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confirmed with the deciphering of the 3-dimensional structure of the ribosome in 2001. Specifically, peptide bond formation, the reaction that binds

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Carole Anastasi, Michael A. Crowe, Matthew W. Powner, John D. Sutherland "Direct Assembly of Nucleoside Precursors from Two- and Three-Carbon Units

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Competition between RNA may have favored the emergence of cooperation between different RNA chains, opening the way for the formation of the first

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Joyce GF, Visser GM, van Boeckel CA, van Boom JH, Orgel LE, van Westrenen J (1984). "Chiral selection in poly(C)-directed synthesis of oligo(G)".

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Vlassov AV, Kazakov SA, Johnston BH, Landweber LF (August 2005). "The RNA world on ice: a new scenario for the emergence of RNA information".

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is that the system of reproduction and metabolism utilized by all extant life involves three distinct types of interdependent macromolecules (

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Anastasi C, Buchet FF, Crowe MA, Parkes AL, Powner MW, Smith JM, Sutherland JD (April 2007). "RNA: prebiotic product, or biotic invention?".

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Some of the difficulties of producing the precursors on earth are bypassed by another alternative or complementary theory for their origin,

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Powner MW, Gerland B, Sutherland JD (May 2009). "Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions".

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together with many proteins. The rRNA molecules are thought responsible for its enzymatic activity, as no amino-acid residues lie within 18

4315: 1640: 1318:(RNAi), where an enzyme-associated guide RNA targets specific mRNA for selective destruction. Likewise, in eukaryotes the maintenance of 7887: 7365: 5846:"Three RNA cells for ribosomal lineages and three DNA viruses to replicate their genomes: a hypothesis for the origin of cellular domain" 2102:

Rich, Alexander (1962). "On the problems of evolution and biochemical information transfer". In Kasha, Michael; Pullman, Bernard (eds.).

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A research project completed in March 2015 by the Sutherland group found that a network of reactions beginning with hydrogen cyanide and

7534: 6030: 416:, and, when the majority of the amino-acid residues in the ribosome were stringently removed, the resulting ribosome retained its full 6063: 4559: 2666:

Forster AC, Symons RH (April 1987). "Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active sites".

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Muller AW (October 2005). "Thermosynthesis as energy source for the RNA World: a model for the bioenergetics of the origin of life".

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which could have linked the chemical components into short peptide and lipid chains as well as short RNA-like chains of nucleotides.

7348: 5156:"A novel virus genome discovered in an extreme environment suggests recombination between unrelated groups of RNA and DNA viruses" 235:

in 1986, in a commentary on how recent observations of the catalytic properties of various forms of RNA fit with this hypothesis.

4894: 1171:) mediate the synthesis of RNA molecules. PAHs are the most common and abundant of the known polyatomic molecules in the visible 5743:

Barry RD (August 1961). "The multiplication of influenza virus. II. Multiplicity reactivation of ultraviolet irradiated virus".

8287: 8046: 7966: 7245: 6166: 1156:) have also been proposed as a starting point, and like PNA, also lack experimental evidence for their respective abiogenesis. 1094:

Another interesting proposal is the idea that RNA synthesis might have been driven by temperature gradients, in the process of

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would be potentially lethal to the protocell (e.g., by blocking replication or inhibiting the function of an essential gene).

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The ability to conjugate an amino acid to the 3'-end of an RNA in order to use its chemical groups or provide a long-branched

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Noller HF, Hoffarth V, Zimniak L (June 1992). "Unusual resistance of peptidyl transferase to protein extraction procedures".

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Kruger, Kelly; Grabowski, Paula J.; Zaug, Arthur J.; Sands, Julie; Gottschling, Daniel E.; Cech, Thomas R. (November 1982).

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of ribozymes, capable of self-replication in about an hour, has been identified. It was produced by molecular competition (

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nucleobases cytosine and uracil under prebiotic conditions, it is thought by some that nucleic acids did not contain these

4528: 7412: 5267:"Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures" 3654: 1828: 8920: 7217: 6216:

Cami J, Bernard-Salas J, Peeters E, Malek SE (September 2010). "Detection of C60 and C70 in a young planetary nebula".

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Riboswitches have been found to act as regulators of gene expression, particularly in bacteria, but also in plants and

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Copley SD, Smith E, Morowitz HJ (December 2007). "The origin of the RNA world: co-evolution of genes and metabolism".

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The RNA world hypothesis is supported by RNA's ability to do all three of to store, to transmit, and to duplicate

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Pascal, Robert (2007), "A scenario starting from the first chemical building blocks", in Reisse, Jacques (ed.),

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Gilker JC, Pavilanis V, Ghys R (June 1967). "Multiplicity reactivation in gamma irradiated influenza viruses".

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The proposal that life on Earth arose from an RNA World is the one most researched in the topic of Abiogenesis.

1087: 969: 2558:"Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena" 1388: 9840: 8870: 7435: 6500: 5038: 1339: 942:

identified three molecular candidates for the bases that might have formed an earliest version of proto-RNA:

911:, including uracil, cytosine, and thymine, have been formed in the laboratory under conditions found only in 845:

The RNA world hypothesis proposes that spontaneous polymerization of ribonucleotides led to the emergence of

1330:, includes a ribonucleoprotein component, although the function of this organelle remains to be elucidated. 9878: 9488: 9169: 8905: 7341: 2611:

Guerrier-Takada, Cecilia; Gardiner, Katheleen; Marsh, Terry; Pace, Norman; Altman, Sidney (December 1983).

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In March 2015, NASA scientists reported that, for the first time, complex DNA and RNA organic compounds of

850: 620:, truncating or permitting transcription respectively. Alternatively, riboswitches may bind or occlude the 320: 62: 9174: 7053:"The RNA world hypothesis: the worst theory of the early evolution of life (except for all the others)(a)" 6148:"The PAH World – Discotic polynuclear aromatic compounds as a mesophase scaffolding at the origin of life" 1124:. If so, life-suitable molecules, originating on Mars, may have later migrated to Earth via mechanisms of 9408: 9164: 8101: 7440: 5562:

Eigen M, Gardiner W, Schuster P, Winkler-Oswatitsch R (April 1981). "The origin of genetic information".

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Flores R, Gago-Zachert S, Serra P, Sanjuán R, Elena SF (2014). "Viroids: survivors from the RNA world?".

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Woese C.R. (1967). The genetic code: The molecular basis for genetic expression. p. 186. Harper & Row

686: 624:, affecting translation. It has been suggested that these originated in an RNA-based world. In addition, 621: 134: 7407: 6669: 6311: 4389: 1252: 654: 7139:

Camprubí E, de Leeuw JW, House CH, Raulin F, Russell MJ, Spang A, Tirumalai MR, Westall F (Dec 2019).

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Diener TO (August 1971). "Potato spindle tuber "virus". IV. A replicating, low molecular weight RNA".

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conditions suggests that it is premature to dismiss the RNA-first scenarios. Suggestions for 'simple'

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Furukawa Y, Chikaraishi Y, Ohkouchi N, Ogawa NO, Glavin DP, Dworkin JP, et al. (December 2019).

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Szathmáry E (June 1999). "The origin of the genetic code: amino acids as cofactors in an RNA world".

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Kumar A, Sharma S, Maurya RA (2010). "Single Nucleotide-Catalyzed Biomimetic Reductive Amination".

4651:"Molecular Precursors of the RNA-World in Space: New Nitriles in the G+0.693−0.027 Molecular Cloud" 2806: 2738: 1195: 733: 6618:"Phosphorylation, oligomerization and self-assembly in water under potential prebiotic conditions" 6147: 4276: 1310:

take place at sites determined by the base pairing between the target RNA and RNA constituents of

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inherently fragile, and they can easily be broken down into their constituent nucleotides through

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Bose T, Fridkin G, Davidovich C, Krupkin M, Dinger N, Falkovich AH, et al. (February 2022).

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Becker S, Feldmann J, Wiedemann S, Okamura H, Schneider C, Iwan K, et al. (October 2019).

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Neveu M, Kim HJ, Benner SA (April 2013). "The "strong" RNA world hypothesis: fifty years old".

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If the RNA world existed, it was probably followed by an age characterized by the evolution of

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Fox GE (2016). "Origins and early evolution of the ribosome". In Hernández G, Jagus R (eds.).

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Callahan MP, Smith KE, Cleaves HJ, Ruzicka J, Stern JC, Glavin DP, et al. (August 2011).

3311:"Origin of life: protoribosome forms peptide bonds and links RNA and protein dominated worlds" 669:, and it happens that this particular base is used as omnipresent energy vehicle in the cell: 499:

to cleave the phosphodiester backbone. The hydroxyl group also forces the ribose into the C3'-

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Since there were no known chemical pathways for the abiogenic synthesis of nucleotides from

9515: 9510: 9386: 8951: 8935: 8560: 7931: 7902: 7783: 7607: 7152: 6972: 6869: 6534: 6406: 6351: 6276: 6225: 6104: 5965: 5857: 5797: 5648: 5571: 5337: 5278: 5101: 4931: 4895:"First Examples Of RNA That Replicates Itself Indefinitely Developed By Scripps Scientists" 4856: 4746: 4672: 4607: 4551: 4473: 4342: 4174: 4119: 4060: 4013: 3903: 3794: 3735: 3684: 3498: 3369: 3360:

Zhang B, Cech TR (November 1997). "Peptide bond formation by in vitro selected ribozymes".

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is suggested to have evolved from RNA molecules that began to catalyze amino acid transfer.

417: 312: 274: 270: 3260:"A vestige of a prebiotic bonding machine is functioning within the contemporary ribosome" 3258:

Krupkin M, Matzov D, Tang H, Metz M, Kalaora R, Belousoff MJ, et al. (October 2011).

901: 8: 9751: 9593: 9549: 9505: 9243: 8895: 8875: 8688: 8378: 7866: 7730: 7705: 7673: 7592: 7450: 1393: 1351: 1206: 994: 986:

Additional evidence supporting the concept of an RNA world has resulted from research on

863: 802: 705: 609: 586: 496: 404:. This is done in modern cells by ribosomes, a complex of several RNA molecules known as 316: 278: 227: 160: 7156: 6976: 6873: 6538: 6523:"Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism" 6410: 6355: 6280: 6229: 6108: 5969: 5861: 5801: 5721: 5652: 5575: 5448: 5341: 5282: 5105: 4935: 4860: 4750: 4676: 4611: 4477: 4346: 4178: 4123: 4108:"Rates of decomposition of ribose and other sugars: implications for chemical evolution" 4064: 4017: 3907: 3739: 3688: 3502: 3373: 3264:

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences

3228: 3175: 3069: 3014: 2914: 2797: 2729: 2471: 2373: 2289: 2229: 2060: 1876: 1784: 1727: 1712:"Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides" 1544: 1529:"Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism" 1436: 690: 9801: 8993: 8915: 8885: 8830: 8707: 8683: 8182: 8116: 7981: 7941: 7792: 7755: 7715: 7694: 7637: 7612: 7467: 7298: 7273: 7122: 7097: 7079: 7052: 7034: 7009: 6996: 6932: 6820: 6793: 6769: 6723: 6696: 6642: 6617: 6555: 6522: 6430: 6397:

Kunin V (October 2000). "A system of two polymerases--a model for the origin of life".

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Nudler E, Mironov AS (January 2004). "The riboswitch control of bacterial metabolism".

3759: 3708: 3585: 3530: 3393: 3337: 3310: 3286: 3259: 3192: 3159: 3135: 3110: 3086: 3053: 3034: 2933: 2898: 2871: 2847:"Selection of an improved RNA polymerase ribozyme with superior extension and fidelity" 2846: 2827: 2759: 2711:"RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension" 2691: 2648: 2593: 2538: 2436: 2393: 2303: 2249: 2154: 2079: 2044: 2025: 1942: 1915: 1896: 1833: 1806: 1749: 1645: 1613: 1588: 1561: 1528: 1504: 1479: 1268: 1153: 1149: 879: 122: 9028: 6881: 5660: 5583: 5360: 5325: 5301: 5266: 4902: 4583:"Detection of the simplest sugar, glycolaldehyde, in a solar-type protostar with ALMA" 4025: 3859:

Tucker BJ, Breaker RR (June 2005). "Riboswitches as versatile gene control elements".

3747: 3487:"Structurally Complex and Highly Active RNA Ligases Derived from Random RNA Sequences" 3424: 2978: 2961: 460: 315:

activity of protein synthesis. Many other ribozyme activities exist; for example, the

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Lamb RA, Choppin PW (1983). "The gene structure and replication of influenza virus".

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Woese CR (1983). The primary lines of descent and the universal ancestor. Chapter in

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Holmes, Bob (2012) "First Glimpse at the birth of DNA" (New Scientist April 12, 2012)

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scenario, the RNA world can serve as a model system for studying the origin of life.

7526: 7000: 6839: 6773: 6253: 6170: 5932: 5090:"Spontaneous formation and base pairing of plausible prebiotic nucleotides in water" 4782: 4627: 3589: 3534: 2831: 2763: 2695: 2652: 2597: 2542: 2440: 2253: 1900: 1810: 9532: 9426: 9059: 9017: 9005: 8925: 8825: 8730: 8678: 8111: 7986: 7951: 7872: 7860: 7820: 7725: 7658: 7293: 7285: 7160: 7117: 7109: 7074: 7064: 7029: 7021: 6980: 6936: 6916: 6877: 6815: 6805: 6751: 6718: 6708: 6637: 6629: 6550: 6542: 6434: 6414: 6369: 6359: 6284: 6233: 6132: 6112: 6008: 5973: 5912: 5875: 5865: 5825: 5805: 5760: 5752: 5717: 5656: 5579: 5535: 5525: 5452: 5444: 5404: 5396: 5355: 5345: 5296: 5286: 5214: 5177: 5167: 5117: 5109: 5062: 4949: 4939: 4872: 4864: 4809: 4754: 4680: 4615: 4491: 4481: 4360: 4350: 4284: 4261: 4241: 4202: 4182: 4137: 4127: 4078: 4068: 4021: 3955: 3950: 3938: 3911: 3894:

Bocobza SE, Aharoni A (October 2008). "Switching the light on plant riboswitches".

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Nunes Palmeira R, Colnaghi M, Harrison SA, Pomiankowski A, Lane N (November 2022).

3081: 3073: 3038: 3018: 2973: 2928: 2918: 2866: 2858: 2811: 2743: 2675: 2624: 2569: 2522: 2485: 2475: 2420: 2397: 2377: 2307: 2293: 2276: 2233: 2181: 2158: 2138: 2074: 2064: 2029: 2009: 1937: 1927: 1880: 1788: 1731: 1681: 1608: 1600: 1556: 1548: 1499: 1491: 1440: 1315: 1256: 1248: 1071: 1050: 666: 555: 339: 334: 66: 6288: 4708: 3915: 2612: 2557: 2424: 1916:"Reviving the RNA World: An Insight into the Appearance of RNA Methyltransferases" 80:. The term also refers to the hypothesis that posits the existence of this stage. 9789: 9483: 9462: 9391: 9194: 8613: 8588: 8126: 8066: 7850: 7750: 7735: 7720: 7627: 7617: 7385: 6666:"Scientists Find Potential "Missing Link" in Chemistry That Led to Life on Earth" 5916: 4798:"RNA-Catalyzed CoA, NAD, and FAD Synthesis from Phosphopantetheine, NMN, and FMN" 3675:

Lindahl T (April 1993). "Instability and decay of the primary structure of DNA".

2103: 1685: 1276: 1095: 943: 859: 793:, was published suggesting building blocks of RNA (adenine, guanine, and related 625: 258: 145: 7289: 7113: 7025: 6713: 2456:"Peptide nucleic acids rather than RNA may have been the first genetic molecule" 1604: 1495: 657:, their formation in prebiotically plausible conditions was reported in 2009; a 9779: 9666: 9537: 9396: 9379: 9184: 9114: 8850: 8815: 8598: 8488: 8453: 8438: 8373: 8368: 8267: 8167: 8086: 8061: 8026: 7971: 7946: 7815: 7663: 7256: 6586:(News). Washington, D.C.: American Association for the Advancement of Science. 6344: