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RNA synthesis by in vitro selected ribozymes for recreating an RNA world.

Martin LL, Unrau PJ, Müller UF - Life (Basel) (2015)

Bottom Line: The RNA world hypothesis states that during an early stage of life, RNA molecules functioned as genome and as the only genome-encoded catalyst.This hypothesis is supported by several lines of evidence, one of which is the in vitro selection of catalytic RNAs (ribozymes) in the laboratory for a wide range of reactions that might have been used by RNA world organisms.These ribozyme classes catalyze nucleoside synthesis, triphosphorylation, and the polymerization of nucleoside triphosphates.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada. lyssam@sfu.ca.

ABSTRACT
The RNA world hypothesis states that during an early stage of life, RNA molecules functioned as genome and as the only genome-encoded catalyst. This hypothesis is supported by several lines of evidence, one of which is the in vitro selection of catalytic RNAs (ribozymes) in the laboratory for a wide range of reactions that might have been used by RNA world organisms. 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. These ribozyme classes catalyze nucleoside synthesis, triphosphorylation, and the polymerization of nucleoside triphosphates. The strengths and weaknesses regarding each ribozyme's possible function in a self-replicating RNA network are described, together with the obstacles that need to be overcome before an RNA world organism can be generated in the laboratory.

No MeSH data available.


Related in: MedlinePlus

Steps in the synthesis of RNA before and during the RNA World. (A) Prior to the emergence of RNA catalysts, abiotic processes led to the generation of RNA polymers (black arrows). After the emergence of RNA catalysts some or all of these reactions were catalyzed by ribozymes (dotted lines); (B) Reactions catalyzed by nucleotide synthase ribozymes. The a15 ribozyme promotes the synthesis of 4SUMP from free 4SUra and PRPP tethered to its 3'-terminus. Similarly the MA ribozyme catalyses the synthesis of 6SGMP from free 6SGua and tethered PRPP; (C) The TPR1 ribozyme promotes the triphosphorylation of its 5'-terminus with trimetaphosphate; (D) Template dependent RNA polymerization is catalyzed by the B6.61 RNAP ribozyme.
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life-05-00247-f002: Steps in the synthesis of RNA before and during the RNA World. (A) Prior to the emergence of RNA catalysts, abiotic processes led to the generation of RNA polymers (black arrows). After the emergence of RNA catalysts some or all of these reactions were catalyzed by ribozymes (dotted lines); (B) Reactions catalyzed by nucleotide synthase ribozymes. The a15 ribozyme promotes the synthesis of 4SUMP from free 4SUra and PRPP tethered to its 3'-terminus. Similarly the MA ribozyme catalyses the synthesis of 6SGMP from free 6SGua and tethered PRPP; (C) The TPR1 ribozyme promotes the triphosphorylation of its 5'-terminus with trimetaphosphate; (D) Template dependent RNA polymerization is catalyzed by the B6.61 RNAP ribozyme.

Mentions: The first catalytic RNA must have arisen in an environment that already executed all steps in a chemical pathway from prebiotically available molecules to RNA polymers—otherwise this catalytic RNA could not have existed (Figure 2A). The chemistry of RNA polymer synthesis before the emergence of RNA World catalysts is poorly understood and has been proposed to occur in several alternative ways. Nucleotide synthesis has been suggested to have proceeded via the glycosidic bond formation between ribose and nucleobases [22,23] or the stepwise assembly of a nucleobase on ribose [24,25]. Many routes of prebiotic nucleotide polymerization have been explored. Some of these routes do not require activation groups on the nucleotides: such as the formation of polymers by the dehydration of nucleoside 5'-monophosphates in lipid environments [26], and the formation of dinucleotides by the reaction of adenosine 2',3'-cyclic phosphate on poly(U) templates [27]. The latter of these studies analyzed the balance between dinucleotide formation and hydrolysis under different conditions, illustrating the thermodynamic challenges of RNA polymerization. In aqueous solution, RNA polymerization is entropically disfavored, making activating groups necessary for the production of long RNA polymers. A range of 5'-phosphate activating groups with variable prebiotic plausibility have been investigated: adenylate [28], cyanide [29], imidazole [30], 2-methyl imidazole [31] and triphosphates [32]. While these forms of chemical activation have provided insight into RNA polymerization, polyphosphates are considered the most prebiotically likely activation groups [33,34]. The polymerization of activated nucleotides into RNA polymers has been explored on the surface of clay minerals [35] or using cations such as Zn2+ [30]. It is currently unclear which of these possibilities, if any, preceded the chemical pathways of the RNA World. The first RNA world organisms likely used existing abiotic chemical pathways and improved on their efficiency and/or selectivity by catalyzing rate-limiting reactions. Later evolutionary stages of RNA World organisms may have modified these pathways to use better suited metabolites essential for RNA replication (Figure 2A). With the onset of the RNA World, vesicle-encapsulated aqueous droplets would have served as the center for an RNA metabolism sustained by ribozymes encoded by an RNA genome [36,37], placing constraints on the chemistry and kinetic stability of nucleotide activation groups in aqueous solution.


RNA synthesis by in vitro selected ribozymes for recreating an RNA world.

Martin LL, Unrau PJ, Müller UF - Life (Basel) (2015)

Steps in the synthesis of RNA before and during the RNA World. (A) Prior to the emergence of RNA catalysts, abiotic processes led to the generation of RNA polymers (black arrows). After the emergence of RNA catalysts some or all of these reactions were catalyzed by ribozymes (dotted lines); (B) Reactions catalyzed by nucleotide synthase ribozymes. The a15 ribozyme promotes the synthesis of 4SUMP from free 4SUra and PRPP tethered to its 3'-terminus. Similarly the MA ribozyme catalyses the synthesis of 6SGMP from free 6SGua and tethered PRPP; (C) The TPR1 ribozyme promotes the triphosphorylation of its 5'-terminus with trimetaphosphate; (D) Template dependent RNA polymerization is catalyzed by the B6.61 RNAP ribozyme.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390851&req=5

life-05-00247-f002: Steps in the synthesis of RNA before and during the RNA World. (A) Prior to the emergence of RNA catalysts, abiotic processes led to the generation of RNA polymers (black arrows). After the emergence of RNA catalysts some or all of these reactions were catalyzed by ribozymes (dotted lines); (B) Reactions catalyzed by nucleotide synthase ribozymes. The a15 ribozyme promotes the synthesis of 4SUMP from free 4SUra and PRPP tethered to its 3'-terminus. Similarly the MA ribozyme catalyses the synthesis of 6SGMP from free 6SGua and tethered PRPP; (C) The TPR1 ribozyme promotes the triphosphorylation of its 5'-terminus with trimetaphosphate; (D) Template dependent RNA polymerization is catalyzed by the B6.61 RNAP ribozyme.
Mentions: The first catalytic RNA must have arisen in an environment that already executed all steps in a chemical pathway from prebiotically available molecules to RNA polymers—otherwise this catalytic RNA could not have existed (Figure 2A). The chemistry of RNA polymer synthesis before the emergence of RNA World catalysts is poorly understood and has been proposed to occur in several alternative ways. Nucleotide synthesis has been suggested to have proceeded via the glycosidic bond formation between ribose and nucleobases [22,23] or the stepwise assembly of a nucleobase on ribose [24,25]. Many routes of prebiotic nucleotide polymerization have been explored. Some of these routes do not require activation groups on the nucleotides: such as the formation of polymers by the dehydration of nucleoside 5'-monophosphates in lipid environments [26], and the formation of dinucleotides by the reaction of adenosine 2',3'-cyclic phosphate on poly(U) templates [27]. The latter of these studies analyzed the balance between dinucleotide formation and hydrolysis under different conditions, illustrating the thermodynamic challenges of RNA polymerization. In aqueous solution, RNA polymerization is entropically disfavored, making activating groups necessary for the production of long RNA polymers. A range of 5'-phosphate activating groups with variable prebiotic plausibility have been investigated: adenylate [28], cyanide [29], imidazole [30], 2-methyl imidazole [31] and triphosphates [32]. While these forms of chemical activation have provided insight into RNA polymerization, polyphosphates are considered the most prebiotically likely activation groups [33,34]. The polymerization of activated nucleotides into RNA polymers has been explored on the surface of clay minerals [35] or using cations such as Zn2+ [30]. It is currently unclear which of these possibilities, if any, preceded the chemical pathways of the RNA World. The first RNA world organisms likely used existing abiotic chemical pathways and improved on their efficiency and/or selectivity by catalyzing rate-limiting reactions. Later evolutionary stages of RNA World organisms may have modified these pathways to use better suited metabolites essential for RNA replication (Figure 2A). With the onset of the RNA World, vesicle-encapsulated aqueous droplets would have served as the center for an RNA metabolism sustained by ribozymes encoded by an RNA genome [36,37], placing constraints on the chemistry and kinetic stability of nucleotide activation groups in aqueous solution.

Bottom Line: The RNA world hypothesis states that during an early stage of life, RNA molecules functioned as genome and as the only genome-encoded catalyst.This hypothesis is supported by several lines of evidence, one of which is the in vitro selection of catalytic RNAs (ribozymes) in the laboratory for a wide range of reactions that might have been used by RNA world organisms.These ribozyme classes catalyze nucleoside synthesis, triphosphorylation, and the polymerization of nucleoside triphosphates.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada. lyssam@sfu.ca.

ABSTRACT
The RNA world hypothesis states that during an early stage of life, RNA molecules functioned as genome and as the only genome-encoded catalyst. This hypothesis is supported by several lines of evidence, one of which is the in vitro selection of catalytic RNAs (ribozymes) in the laboratory for a wide range of reactions that might have been used by RNA world organisms. 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. These ribozyme classes catalyze nucleoside synthesis, triphosphorylation, and the polymerization of nucleoside triphosphates. The strengths and weaknesses regarding each ribozyme's possible function in a self-replicating RNA network are described, together with the obstacles that need to be overcome before an RNA world organism can be generated in the laboratory.

No MeSH data available.


Related in: MedlinePlus