Selective Pressures on RNA Hairpins In Vivo and In Vitro |
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Authors: | Alexander P Gultyaev FHD van Batenburg Cornelis WA Pleij |
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Institution: | (1) Group Theoretical Biology and Phylogenetics, Institute of Evolutionary and Ecological Sciences, Leiden University, Kaiserstraat 63, 2311 GP Leiden, The Netherlands, NL;(2) Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands, NL |
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Abstract: | Comparison of the most stable potential hairpins in the sequences of natural ribozymes with those in the randomized sequences
has revealed that the hairpin loop energies are lower than expected by chance. Although these hairpins are not necessarily
parts of functional structures, there is a selective pressure to diminish the destabilizing free energies of the hairpin loops.
In contrast, no significant bias is observed in the stacking values of the most stable stems. In the ribozymes isolated in
vitro the loops of potential hairpins are closer to random values, which can result in less efficient folding rates. Furthermore,
the effects of kinetic traps seem to be more significant in the folding pathways of the in vitro isolates due to a potential
to form stable stacks incompatible with the functional folds. Similarly to natural ribozyme sequences, the untranslated regions
of viral RNAs also form hairpins with relatively low loop free energies. These evolutionary trends suggest ways for efficient
engineering of improved RNA constructs on the basis of analysis of in vitro isolates and approaches for the search of regions
coding for functional RNA structures in large genome sequences.
Received: 12 January 2001 / Accepted: 21 May 2001 |
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Keywords: | : RNA structure — Evolutionary constraints — SELEX — Folding kinetics — Ribozymes |
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