A cross-chiral RNA polymerase ribozyme

Abstract

Thirty years ago it was shown that the non-enzymatic, template-directed polymerization of activated mononucleotides proceeds readily in a homochiral system, but is severely inhibited by the presence of the opposing enantiomer.1 This finding poses a severe challenge for the spontaneous emergence of RNA-based life, and has led to the suggestion that either RNA was preceded by some other genetic polymer that is not subject to chiral inhibition2 or chiral symmetry was broken through chemical processes prior to the origin of RNA-based life.3,4 Once an RNA enzyme arose that could catalyze the polymerization of RNA, it would have been possible to distinguish among the two enantiomers, enabling RNA replication and RNA-based evolution to occur. It is commonly thought that the earliest RNA polymerase and its substrates would have been of the same handedness, but this is not necessarily the case. Replicating D-and L-RNA molecules may have emerged together, based on the ability of structured RNAs of one handedness to catalyze the templated polymerization of activated mononucleotides of the opposite handedness. Such a cross-chiral RNA polymerase has now been developed using in vitro evolution. The D-RNA enzyme, consisting of 83 nucleotides, catalyzes the joining of L-mono- or oligonucleotide substrates on a complementary L-RNA template, and similarly for the L-enzyme with D-substrates and a D-template. Chiral inhibition is avoided because the 106-fold rate acceleration of the enzyme only pertains to cross-chiral substrates. The enzyme's activity is sufficient to generate full-length copies of its enantiomer through the templated joining of 11 component oligonucleotides.

Mechanically Induced Homochirality in Nucleated Enantioselective Polymerization

“…In biopolymers, the diastereoselective selection towards homochirality has been confirmed by experimental reports on the polymerization of amino acids and nucleotides from racemic mixtures where, after a certain chain length, the diastereoselective formation of homochiral chains occur preferentially. 13,17,41,42 In light of these results, it is difficult to conceive how such systems, where homochiral interactions dominate, can simultaneously accommodate heterochiral cross inhibition reactions. In this respect, the SMSB mechanism operating in the Viedma deracemization experiment 43 The mechanical breakage (which is an external energy input to the system) of the longer chains is a recycling of lower to higher energy compounds.…”

Spontaneous mirror symmetry breaking and origin of biological homochirality

“…[67] with those of ref. [43]). This suggests an advantage of asymmetry in evolution leading to the chemical systems constituting protocells.…”

Chiral Symmetry Breaking in Peptide Systems During Formation of Life on Earth

“…On the opposite side, deracemization utilizes a phase transition process of crystallization and nonlinearity due to the rate of crystallization being proportional to the surface area of the crystals (Hein et al 2012;van der Meijden et al 2009;Noorduin et al 2010). In contrast to basic chemical reactions, which are polynomial functions of concentrations, a phase transition, if viewed as a mathematical function, exhibits some discontinuity.…”

“…The number of works in this area could be made a subject of a separate research. Vast number of models of chiral symmetry breaking were proposed over the years and numerous experiments were performed, for example (Frank 1953;Avetisov and Goldanskii 1996;Plasson et al 2004Plasson et al , 2007Saito and Hyuga 2004;Weissbuch et al 2005;Brandenburg et al 2007; van der Meijden et al 2009;Noorduin et al 2010;Blackmond 2011;Coveney et al 2012;Hein et al 2012;Ribó et al 2013;Konstantinova 2013, 2014), and many others. However, most, if not all, theories and experiments related to chiral symmetry breaking during formation of life on Earth considered only a very limited number of substances and reactions, whereas the actual number of possible substances and reactions among them must have been extremely large, as we will soon discuss.…”

“…Alternative models of chiral symmetry breaking are based on inter-conversion of enantiomers. These models can be grouped into two classes: the models based on epimerization (Plasson et al 2004(Plasson et al , 2007Weissbuch et al 2005;Brandenburg et al 2007) and the models based on the deracemization process (Hein et al 2012;van der Meijden et al 2009;Noorduin et al 2010).…”