Improved polymerase ribozyme efficiency on hydrophobic assemblies

Müller, Ulrich F.; Bartel, David P.

doi:10.1261/rna.494508

Cited by 41 publications

(36 citation statements)

References 51 publications

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“…1A,B tB6.61, would be predicted to be on the ''top'' of the Class I ligase tripod, making it difficult for a tethered PT to be correctly positioned into the polymerase active site. These findings, which constrain the orientation of the PT, are consistent with an independent study in which the PT was co-localized nonspecifically to the Round 18 RNA polymerase ribozyme via hydrophobic anchors and where a three-to 20-fold increase in catalytic rate was observed (Muller and Bartel 2008).…”

Section: Resultssupporting

confidence: 90%

Characterization of the B6.61 polymerase ribozyme accessory domain

Wang¹,

Cheng²,

Unrau³

2011

RNA

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The ''RNA world'' hypothesis rests on the assumption that RNA polymerase ribozymes can replicate RNA without the use of protein. In the laboratory, in vitro selection has been used to create primitive versions of such polymerases. The best variant to date is a ribozyme called B6.61 that can extend a RNA primer template by 20 nucleotides (nt). This polymerase has two domains: the recently crystallized Class I ligase core, responsible for phosphodiester bond formation, and the poorly characterized accessory domain that makes polymerization possible. Here we find that the accessory domain is specified by a 37-nt bulged stem-loop structure. The accessory domain is positioned by a tertiary interaction between the terminal AL4 loop of the accessory and the J3/4 triloop found within the ligase core. This docking interaction is associated with an unwinding of the A3 and A4 helixes that appear to facilitate the correct positioning of an essential 8-nt purine bulge found between the two helices. This, together with other constraints inferred from tethering the accessory domain to a range of sites on the ligase core, indicates that the accessory domain is draped over the vertex of the ligase core tripod structure. This geometry suggests how the purine bulge in the polymerase replaces the P2 helix in the Class I ligase with a new structure that may facilitate the stabilization of incoming nucleotide triphosphates.

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Section: Resultssupporting

confidence: 90%

Characterization of the B6.61 polymerase ribozyme accessory domain

Wang¹,

Cheng²,

Unrau³

2011

RNA

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“…It is of particular interest how the evolution of the class I ligase ribozyme (Bartel and Szostak 1993), appended with a track of 76 random nucleotides at its 39 end, allowed the selection of a 189-nt-long template-dependent RNA polymerase ribozyme (Johnston et al 2001). The efficiency of this ribozyme has been improved by further in vitro evolution (Zaher and Unrau 2007), as well as by appending it to micelle-forming hydrophobic molecules (Müller and Bartel 2008).…”

Section: A Stepwise Model For the Origin Of The Rna Worldmentioning

confidence: 99%

The dawn of the RNA World: Toward functional complexity through ligation of random RNA oligomers

Briones¹,

Stich²,

Manrubia³

2009

RNA

103

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A main unsolved problem in the RNA World scenario for the origin of life is how a template-dependent RNA polymerase ribozyme emerged from short RNA oligomers obtained by random polymerization on mineral surfaces. A number of computational studies have shown that the structural repertoire yielded by that process is dominated by topologically simple structures, notably hairpin-like ones. A fraction of these could display RNA ligase activity and catalyze the assembly of larger, eventually functional RNA molecules retaining their previous modular structure: molecular complexity increases but template replication is absent. This allows us to build up a stepwise model of ligation-based, modular evolution that could pave the way to the emergence of a ribozyme with RNA replicase activity, step at which information-driven Darwinian evolution would be triggered.

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“…This diffusion limitation is a prerequisite for Darwinian evolution 6 , because it averts dissipation of the replicase genotype by fruitless replication of unrelated (and most likely inactive) RNA sequences, and curbs the rise of fastreplicating RNA parasites 7 . Although a range of structured environments, including micelles, membraneous vesicles, porous rocks or even aerosol droplets [8][9][10][11][12] , have been proposed as protocellular media capable of providing compartmentalization, their ability to support RNA replication and protect RNA from degradation is unclear.…”

mentioning

confidence: 99%

Ice as a protocellular medium for RNA replication

et al. 2010

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A crucial transition in the origin of life was the emergence of an informational polymer capable of self-replication and its compartmentalization within protocellular structures. We show that the physicochemical properties of ice, a simple medium widespread on a temperate early Earth, could have mediated this transition prior to the advent of membraneous protocells. Ice not only promotes the activity of an RNA polymerase ribozyme but also protects it from hydrolytic degradation, enabling the synthesis of exceptionally long replication products. Ice furthermore relieves the dependence of RNA replication on prebiotically implausible substrate concentrations, while providing quasicellular compartmentalization within the intricate microstructure of the eutectic phase. Eutectic ice phases had previously been shown to promote the de novo synthesis of nucleotide precursors, as well as the condensation of activated nucleotides into random RNA oligomers. Our results support a wider role for ice as a predisposed environment, promoting all the steps from prebiotic synthesis to the emergence of RNA self-replication and precellular Darwinian evolution.

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Improved polymerase ribozyme efficiency on hydrophobic assemblies

Cited by 41 publications

References 51 publications

Characterization of the B6.61 polymerase ribozyme accessory domain

Characterization of the B6.61 polymerase ribozyme accessory domain

The dawn of the RNA World: Toward functional complexity through ligation of random RNA oligomers

Ice as a protocellular medium for RNA replication

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