A Promiscuous Ribozyme Promotes Nucleotide Synthesis in Addition to Ribose Chemistry

Lau, Matthew W.L.; Unrau, Peter J.

doi:10.1016/j.chembiol.2009.07.005

Cited by 35 publications

(27 citation statements)

References 41 publications

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“…However, the epigenetic interactions that generated these paths were pleiotropic effects such as increased protein aggregation and reduced thermodynamic stability, in contrast to the cooperativity of RNA mutations in our study, which was probably caused by a single factor, binding to the Rho protein. 2 Other studies found that catalytic promiscuity can help in the evolution of a new function both in proteins (65,66) and in RNAs (67). At present, the most powerful experimental system to study macromolecular evolution appears to be phage-assisted continuous evolution (68).…”

Section: Discussionmentioning

confidence: 99%

Low Selection Pressure Aids the Evolution of Cooperative Ribozyme Mutations in Cells

Amini

Müller

2013

Journal of Biological Chemistry

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Background: Ribozyme evolution experiments in cells can help our understanding of natural RNA evolution. Results: During an experimental RNA evolution, the emergence of four cooperative mutations was more efficient under low than under high selection pressure. Conclusion: Low selective pressure can facilitate the evolution of cooperative RNA mutations. Significance: Understanding RNA evolution in biology requires understanding the effects of evolutionary parameters in cells.

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Section: Discussionmentioning

confidence: 99%

Low Selection Pressure Aids the Evolution of Cooperative Ribozyme Mutations in Cells

Amini

Müller

2013

Journal of Biological Chemistry

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“…Small metabolic repertoire and promiscuous ribozymes (e.g. 190 ) were the norm. The invention of the chromosome seems to be the pinnacle of the RNA world, as from its very beginning it was striving for this elusive target (see Section I/3.…”

Section: Iii/2 Enzymatizationmentioning

confidence: 99%

“…Kinase ribozymes 187 could produce the D-ribose-5-phosphate and then 5-phospho-D-ribose-1-diphosphate (PRPP). Ribozymes can catalyse the formation of the glycosidic bond between PRPP and a pyrimidine [188][189][190] or a purine 190,191 nucleobase. Moreover, almost all biologically important reactions could be catalysed by ribozymes to some extent 36 .…”

Section: Iii/2 Enzymatizationmentioning

confidence: 99%

The dynamics of the RNA world: insights and challenges

Kun

Szilágyi

Könnyű

et al. 2015

Annals of the New York Academy of Sciences

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The problem of the origin of life is not only one of structure but also that of dynamics. Ever since the seminal result of Manfred Eigen in 1971 showing that early template replication suffers from an error threshold, research has tackled the issue of how early genomes could have been dynamically stable without highly evolved mechanisms such as accurate replication and chromosomes. We review the theory of the origin, maintenance and enhancement of the RNA world as an evolving population of dynamical systems. Investigation of sequence space has revealed how structures are allocated in sequence space and how this affects the nature of the error threshold that sets the selectively maintainable genome length. New applications of old dynamical theory are still possible: the application of Gause's principle of competitive exclusion, based on resource utilisation, to RNA replication predicts that at most four pairs (plus and minus strands) can stably be maintained on four nucleotides. Other mechanisms of early template coexistence should be regarded as additional means to raise the number of coexisting species above the number set by the competitive exclusion principle. One such example is the hypercycle in which templates were postulated to help replication of the next member in a cycle superimposed on individual replication cycles. Although the hypercycle is ecologically unstable it is evolutionarily unstable because it cannot efficiently compete against emerging parasites. Population structure can modify this conclusion but not without further qualification. The simplest form of population structure is limited diffusion on a surface. This simple mechanism can ensure the coexistence of competing ribozymes contributing to surface metabolism as well as the spread of efficient replicases despite the parasite problem. Hypercyclescan only be saved by active compartmentalization when replicators are enclosed in reproducing protocells. Once there are protocells there is no need for internal hypercyclic organization, however. Finally we review two crucial adaptations that enhanced the RNA world: chromosomes and enzymatic metabolism. Interestingly, it was shown that these two have been presumably coevolutionarily linked because protocells harbouring unlinked, competing ribozymes are better off if the ribozymes remain inefficient but generalists. The appearance of chromosomes alleviates intragenomic conflict and is enabling constraint for the emergence of specific and efficient enzymes.The possibility of an RNA world, a period in the origin of life on Earth, when RNA molecules acted both as enzymes and as genetic material, was suggested well before the name was coined by Gilbert in 1986 1 . The history of the research on the origin of life 2 tells us that the potential prebiotic importance of RNA was suggested as early as in the late 50's. When it became established that living cells harbour much more RNA than DNA some biologist have proposed that RNA preceded DNA during evolution 3,4 . The discovery of the details of protein ...

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“…Recently we made the interesting discovery that a ribozyme selected for its ability to mediate chemistry between ribose and 6-thioguanosine could also promote purine nucleotide synthesis when the ribose substrate was substituted with PRPP (Lau and Unrau 2009). This promiscuous ribozyme suggests that metabolically relevant ribozymes making use of a small metabolite such as ribose could have easily evolved to promote nucleotide synthesis with PRPP.…”

Section: Abiotic Nucleotide Synthesismentioning

confidence: 99%

“…Given the fundamental importance of this chemistry to modern metabolism and its potential compatibility with abiotic supplies of ribose and nucleobases (Lau and Unrau 2009), the ability of RNA to mediate such chemistry serves as a potential bridge between the abiotic and biotic RNAWorld of nucleotide synthesis. However, the chemistry of glycosidic bond formation presents a number of hurdles for RNA catalysts.…”

Section: Abiotic Nucleotide Synthesismentioning

confidence: 99%

Closing the Circle: Replicating RNA with RNA

Cheng¹,

Unrau²

2010

Cold Spring Harbor Perspectives in Biology

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How life emerged on this planet is one of the most important and fundamental questions of science. Although nearly all details concerning our origins have been lost in the depths of time, there is compelling evidence to suggest that the earliest life might have exploited the catalytic and self-recognition properties of RNA to survive. If an RNA based replicating system could be constructed in the laboratory, it would be much easier to understand the challenges associated with the very earliest steps in evolution and provide important insight into the establishment of the complex metabolic systems that now dominate this planet. Recent progress into the selection and characterization of ribozymes that promote nucleotide synthesis and RNA polymerization are discussed and outstanding problems in the field of RNA-mediated RNA replication are summarized.

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A Promiscuous Ribozyme Promotes Nucleotide Synthesis in Addition to Ribose Chemistry

Cited by 35 publications

References 41 publications

Low Selection Pressure Aids the Evolution of Cooperative Ribozyme Mutations in Cells

Low Selection Pressure Aids the Evolution of Cooperative Ribozyme Mutations in Cells

The dynamics of the RNA world: insights and challenges

Closing the Circle: Replicating RNA with RNA

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