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The Paradox of Dual Roles in the RNA World: Resolving the Conflict Between Stable Folding and Templating Ability

Identifieur interne : 002101 ( Main/Exploration ); précédent : 002100; suivant : 002102

The Paradox of Dual Roles in the RNA World: Resolving the Conflict Between Stable Folding and Templating Ability

Auteurs : Nikola A. Ivica [États-Unis] ; Benedikt Obermayer [États-Unis, Allemagne] ; Gregory W. Campbell [États-Unis] ; Sudha Rajamani [États-Unis] ; Ulrich Gerland [Allemagne] ; Irene A. Chen [États-Unis]

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RBID : ISTEX:BD20E8A05FF75AFB7EB758627CB0A76ECEB0F671

English descriptors

Abstract

Abstract: The hypothesized dual roles of RNA as both information carrier and biocatalyst during the earliest stages of life require a combination of features: good templating ability (for replication) and stable folding (for ribozymes). However, this poses the following paradox: well-folded sequences are poor templates for copying, but poorly folded sequences are unlikely to be good ribozymes. Here, we describe a strategy to overcome this dilemma through G:U wobble pairing in RNA. Unlike Watson–Crick base pairs, wobble pairs contribute highly to the energetic stability of the folded structure of their sequence, but only slightly, if at all, to the stability of the folded reverse complement. Sequences in the RNA World might thereby combine stable folding of the ribozyme with an unstructured, reverse-complementary genome, resulting in a “division of labor” between the strands. We demonstrate this strategy using computational simulations of RNA folding and an experimental model of early replication, nonenzymatic template-directed RNA primer extension. Additional study is needed to solve other problems associated with a complete replication cycle, including separation of strands after copying. Interestingly, viroid RNA sequences, which have been suggested to be relics of an RNA World (Diener, Proc Natl Acad Sci USA 86:9370–9374, 1989), also show significant asymmetry in folding energy between the infectious (+) and template (−) strands due to G:U pairing, suggesting that this strategy may even be used by replicators in the present day.

Url:
DOI: 10.1007/s00239-013-9584-x


Affiliations:


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