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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

Pyrimidine and purine nucleotide synthase ribozymes show good substrate discrimination. The arrows point to reaction efficiencies for ribozymes with the indicated substrate molecule: red arrows indicate the MA purine nucleotide synthetase ribozyme reaction efficiencies, purple indicates the RA purine nucleotide synthetase ribozyme, blue indicates the Family A pyrimidine nucleotide synthethase ribozyme and green indicates the improved a15 ribozyme derived from the Family A ribozyme by reselection. In the box nucleobases for which no activity was detected are shown.
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life-05-00247-f003: Pyrimidine and purine nucleotide synthase ribozymes show good substrate discrimination. The arrows point to reaction efficiencies for ribozymes with the indicated substrate molecule: red arrows indicate the MA purine nucleotide synthetase ribozyme reaction efficiencies, purple indicates the RA purine nucleotide synthetase ribozyme, blue indicates the Family A pyrimidine nucleotide synthethase ribozyme and green indicates the improved a15 ribozyme derived from the Family A ribozyme by reselection. In the box nucleobases for which no activity was detected are shown.

Mentions: Whether or not a nucleotide synthase ribozyme had measurable nucleobase binding affinity, all families of nucleotide synthetase ribozymes were extremely sensitive to nucleobase modification and showed surprising parallels to the substrate preferences of highly evolved protein nucleotide synthase enzymes. For example, the family A pyrimidine nucleotide synthetase ribozyme was ~10,000 times slower with uracil than with 4-thiouracil and reactivity with 2-thiocytosine, 2-thiopyrimidine, 2-thiopyridine and 5-carboxy-2-thiouracil could not be detected (Figure 3). In contrast, the MA purine nucleotide synthetase ribozyme was 600 to 3000 times slower when incubated with 6-thiopurine than with 6-thioguanine; while the RA purine nucleotide synthase ribozyme was 5 to 10 times slower still. As these purine nucleotide synthetase ribozymes were much slower with other purine modifications this indicates a lack of substrate discrimination at the 2-position. A similar situation is seen with the protein enzyme HGPTase, which is also unable to discriminate between guanine and hypoxanthine [56]. Similar patterns are seen in guanine binding riboswitches [57]. That two purine nucleotide synthase ribozymes share patterns in common with these naturally selected protein and RNA systems suggests that a single optimal strategy to specifically recognize guanine by hydrogen bonding and stacking interactions exists in nature.


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

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

Pyrimidine and purine nucleotide synthase ribozymes show good substrate discrimination. The arrows point to reaction efficiencies for ribozymes with the indicated substrate molecule: red arrows indicate the MA purine nucleotide synthetase ribozyme reaction efficiencies, purple indicates the RA purine nucleotide synthetase ribozyme, blue indicates the Family A pyrimidine nucleotide synthethase ribozyme and green indicates the improved a15 ribozyme derived from the Family A ribozyme by reselection. In the box nucleobases for which no activity was detected are shown.
© Copyright Policy
Related In: Results  -  Collection

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

life-05-00247-f003: Pyrimidine and purine nucleotide synthase ribozymes show good substrate discrimination. The arrows point to reaction efficiencies for ribozymes with the indicated substrate molecule: red arrows indicate the MA purine nucleotide synthetase ribozyme reaction efficiencies, purple indicates the RA purine nucleotide synthetase ribozyme, blue indicates the Family A pyrimidine nucleotide synthethase ribozyme and green indicates the improved a15 ribozyme derived from the Family A ribozyme by reselection. In the box nucleobases for which no activity was detected are shown.
Mentions: Whether or not a nucleotide synthase ribozyme had measurable nucleobase binding affinity, all families of nucleotide synthetase ribozymes were extremely sensitive to nucleobase modification and showed surprising parallels to the substrate preferences of highly evolved protein nucleotide synthase enzymes. For example, the family A pyrimidine nucleotide synthetase ribozyme was ~10,000 times slower with uracil than with 4-thiouracil and reactivity with 2-thiocytosine, 2-thiopyrimidine, 2-thiopyridine and 5-carboxy-2-thiouracil could not be detected (Figure 3). In contrast, the MA purine nucleotide synthetase ribozyme was 600 to 3000 times slower when incubated with 6-thiopurine than with 6-thioguanine; while the RA purine nucleotide synthase ribozyme was 5 to 10 times slower still. As these purine nucleotide synthetase ribozymes were much slower with other purine modifications this indicates a lack of substrate discrimination at the 2-position. A similar situation is seen with the protein enzyme HGPTase, which is also unable to discriminate between guanine and hypoxanthine [56]. Similar patterns are seen in guanine binding riboswitches [57]. That two purine nucleotide synthase ribozymes share patterns in common with these naturally selected protein and RNA systems suggests that a single optimal strategy to specifically recognize guanine by hydrogen bonding and stacking interactions exists in nature.

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