Frequency of RNA–RNA interaction in a model of the RNA World

Abstract

The RNA World model for prebiotic evolution posits the selection of catalytic/template RNAs from random populations. The mechanisms by which these random populations could be generated de novo are unclear. Non-enzymatic and RNA-catalyzed nucleic acid polymerizations are poorly processive, which means that the resulting short-chain RNA population could contain only limited diversity. Nonreciprocal recombination of smaller RNAs provides an alternative mechanism for the assembly of larger species with concomitantly greater structural diversity; however, the frequency of any specific recombination event in a random RNA population is limited by the low probability of an encounter between any two given molecules. This low probability could be overcome if the molecules capable of productive recombination were redundant, with many nonhomologous but functionally equivalent RNAs being present in a random population. Here we report fluctuation experiments to estimate the redundancy of the set of RNAs in a population of random sequences that are capable of non-Watson-Crick interaction with another RNA. Parallel SELEX experiments showed that at least one in 10 6 random 20-mers binds to the P5.1 stem-loop of Bacillus subtilis RNase P RNA with affinities equal to that of its naturally occurring partner. This high frequency predicts that a single RNA in an RNA World would encounter multiple interacting RNAs within its lifetime, supporting recombination as a plausible mechanism for prebiotic RNA evolution. The large number of equivalent species implies that the selection of any single interacting species in the RNA World would be a contingent event, i.e., one resulting from historical accident.

Ribozyme Activity of RNA Nonenzymatically Polymerized from 3′,5′-Cyclic GMP

“…Pioneering reports of RNA recombination have appeared [7][8][9][10][11][12]. With the possible exception of the systems described in [13][14][15], the reactions reported so far are not simple and robust enough to be of likely prebiotic relevance.…”

Complexity through Recombination: From Chemistry to Biology

“…Striggles et al examined the potential involvement of functional redundancy in a random population of RNAs [33]. A small RNA stem-loop domain of Type II ribonuclease P RNA was used as bait in a SELEX experiment to identify RNAs from a library containing 20 randomized positions that could bind to it.…”

“…Elongation by adding fragments together can be achieved in a more rapid manner than by adding one nucleotide at the time [12,15,33]. This is because, compared to a phosphoanhydride bond, the α,β-phosphodiester bond is kinetically stable, with a k hydrolysis of approximately 10 -10 per minute, at pH 7 and 37 °C in the common aqueous environments.…”

“…For example, the best RNA replicase activity demonstrated to date with a derivative of the class ligase ribozyme requires 5 μM ribozyme and 4 mM of each rNTP to achieve the maximal primer extension seen (20 nt in 24 h) [24]. This underscores the need for an alternative means of chain lengthening, something that recombination can provide with relative ease [15,33]. in the random population.…”

The elusive quest for RNA knots

“…RNA-RNA interactions have often been proposed to be critical to maintaining the physical integrity of networks of distinct sequences. [29][30][31] Typically these interactions have focused solely on secondary structure interactions, but many environments on an early Earth could have experienced rather extreme temperature fluctuations that could disrupt weak basepairing. More severe entanglements such as knotsbut without covalent bondingwould have been a means to preserve spatial sympatry of RNA network individuals in harsh environments.…”