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227 Views of RNA: Is RNA Unique in Its Chemical Isomer Space?

Cleaves HJ, Meringer M, Goodwin J - Astrobiology (2015)

Bottom Line: However, to date no one-pot reaction has been shown capable of yielding RNA monomers from likely prebiotically abundant starting materials, though this does not rule out the possibility that simpler, more easily prebiotically accessible nucleic acids may have preceded RNA.The resulting structures are then evaluated by using molecular descriptors typically applied in quantitative structure-property relationship (QSPR) studies and predicted physicochemical properties.We conclude that ribonucleosides may have competed with a multitude of alternative structures whose potential proto-biochemical roles and abiotic syntheses remain to be explored.

View Article: PubMed Central - PubMed

Affiliation: 1 Earth-Life Science Institute (ELSI), Tokyo Institute of Technology , Tokyo, Japan .

ABSTRACT
Ribonucleic acid (RNA) is one of the two nucleic acids used by extant biochemistry and plays a central role as the intermediary carrier of genetic information in transcription and translation. If RNA was involved in the origin of life, it should have a facile prebiotic synthesis. A wide variety of such syntheses have been explored. However, to date no one-pot reaction has been shown capable of yielding RNA monomers from likely prebiotically abundant starting materials, though this does not rule out the possibility that simpler, more easily prebiotically accessible nucleic acids may have preceded RNA. Given structural constraints, such as the ability to form complementary base pairs and a linear covalent polymer, a variety of structural isomers of RNA could potentially function as genetic platforms. By using structure-generation software, all the potential structural isomers of the ribosides (BC5H9O4, where B is nucleobase), as well as a set of simpler minimal analogues derived from them, that can potentially serve as monomeric building blocks of nucleic acid-like molecules are enumerated. Molecules are selected based on their likely stability under biochemically relevant conditions (e.g., moderate pH and temperature) and the presence of at least two functional groups allowing the monomers to be incorporated into linear polymers. The resulting structures are then evaluated by using molecular descriptors typically applied in quantitative structure-property relationship (QSPR) studies and predicted physicochemical properties. Several databases have been queried to determine whether any of the computed isomers had been synthesized previously. Very few of the molecules that emerge from this structure set have been previously described. We conclude that ribonucleosides may have competed with a multitude of alternative structures whose potential proto-biochemical roles and abiotic syntheses remain to be explored.

No MeSH data available.


The molecular structures of RNA and DNA and their components. (A) The sugars ribose and deoxyribose and their atom-numbering conventions. Note the stereochemistry of the bonds between the ring and its substituents. (B) The nitrogen heterocycles used in RNA [adenine (A), uracil (U), guanine (G), and cytosine (C)] and DNA [A, G, C, and thymine (T)] and their ring-atom-numbering conventions. (C and D) The structures of phosphate-linked RNA and DNA. (E) A simplified generic nucleoside analog structure.
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f1: The molecular structures of RNA and DNA and their components. (A) The sugars ribose and deoxyribose and their atom-numbering conventions. Note the stereochemistry of the bonds between the ring and its substituents. (B) The nitrogen heterocycles used in RNA [adenine (A), uracil (U), guanine (G), and cytosine (C)] and DNA [A, G, C, and thymine (T)] and their ring-atom-numbering conventions. (C and D) The structures of phosphate-linked RNA and DNA. (E) A simplified generic nucleoside analog structure.

Mentions: The molecular solutions life has arrived at for information storage, in the form of DNA and RNA (Fig. 1), are likely evolutionarily optimized with regard to various constraints, including stability, ability to encode information, and ability to compact it in small spaces, such as cells. These requirements can likely only be met by certain molecules given the rules of organic chemistry, though the set of possible molecules could be very large. If there were alternative molecules that could better fulfill these criteria, then extant genetic systems could be considered suboptimal. It is of interest to understand whether biology's solution to these various problems is optimal, suboptimal, or arbitrary. One way to explore this is with structure generation software and in silico property screening.


227 Views of RNA: Is RNA Unique in Its Chemical Isomer Space?

Cleaves HJ, Meringer M, Goodwin J - Astrobiology (2015)

The molecular structures of RNA and DNA and their components. (A) The sugars ribose and deoxyribose and their atom-numbering conventions. Note the stereochemistry of the bonds between the ring and its substituents. (B) The nitrogen heterocycles used in RNA [adenine (A), uracil (U), guanine (G), and cytosine (C)] and DNA [A, G, C, and thymine (T)] and their ring-atom-numbering conventions. (C and D) The structures of phosphate-linked RNA and DNA. (E) A simplified generic nucleoside analog structure.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4523004&req=5

f1: The molecular structures of RNA and DNA and their components. (A) The sugars ribose and deoxyribose and their atom-numbering conventions. Note the stereochemistry of the bonds between the ring and its substituents. (B) The nitrogen heterocycles used in RNA [adenine (A), uracil (U), guanine (G), and cytosine (C)] and DNA [A, G, C, and thymine (T)] and their ring-atom-numbering conventions. (C and D) The structures of phosphate-linked RNA and DNA. (E) A simplified generic nucleoside analog structure.
Mentions: The molecular solutions life has arrived at for information storage, in the form of DNA and RNA (Fig. 1), are likely evolutionarily optimized with regard to various constraints, including stability, ability to encode information, and ability to compact it in small spaces, such as cells. These requirements can likely only be met by certain molecules given the rules of organic chemistry, though the set of possible molecules could be very large. If there were alternative molecules that could better fulfill these criteria, then extant genetic systems could be considered suboptimal. It is of interest to understand whether biology's solution to these various problems is optimal, suboptimal, or arbitrary. One way to explore this is with structure generation software and in silico property screening.

Bottom Line: However, to date no one-pot reaction has been shown capable of yielding RNA monomers from likely prebiotically abundant starting materials, though this does not rule out the possibility that simpler, more easily prebiotically accessible nucleic acids may have preceded RNA.The resulting structures are then evaluated by using molecular descriptors typically applied in quantitative structure-property relationship (QSPR) studies and predicted physicochemical properties.We conclude that ribonucleosides may have competed with a multitude of alternative structures whose potential proto-biochemical roles and abiotic syntheses remain to be explored.

View Article: PubMed Central - PubMed

Affiliation: 1 Earth-Life Science Institute (ELSI), Tokyo Institute of Technology , Tokyo, Japan .

ABSTRACT
Ribonucleic acid (RNA) is one of the two nucleic acids used by extant biochemistry and plays a central role as the intermediary carrier of genetic information in transcription and translation. If RNA was involved in the origin of life, it should have a facile prebiotic synthesis. A wide variety of such syntheses have been explored. However, to date no one-pot reaction has been shown capable of yielding RNA monomers from likely prebiotically abundant starting materials, though this does not rule out the possibility that simpler, more easily prebiotically accessible nucleic acids may have preceded RNA. Given structural constraints, such as the ability to form complementary base pairs and a linear covalent polymer, a variety of structural isomers of RNA could potentially function as genetic platforms. By using structure-generation software, all the potential structural isomers of the ribosides (BC5H9O4, where B is nucleobase), as well as a set of simpler minimal analogues derived from them, that can potentially serve as monomeric building blocks of nucleic acid-like molecules are enumerated. Molecules are selected based on their likely stability under biochemically relevant conditions (e.g., moderate pH and temperature) and the presence of at least two functional groups allowing the monomers to be incorporated into linear polymers. The resulting structures are then evaluated by using molecular descriptors typically applied in quantitative structure-property relationship (QSPR) studies and predicted physicochemical properties. Several databases have been queried to determine whether any of the computed isomers had been synthesized previously. Very few of the molecules that emerge from this structure set have been previously described. We conclude that ribonucleosides may have competed with a multitude of alternative structures whose potential proto-biochemical roles and abiotic syntheses remain to be explored.

No MeSH data available.