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Compact and ordered collapse of randomly generated RNA sequences

Nature Structural & Molecular Biology volume 12, pages 1130–1136 (2005)Cite this article

Abstract

As the raw material for evolution, arbitrary RNA sequences represent the baseline for RNA structure formation and a standard to which evolved structures can be compared. Here, we set out to probe, using physical and chemical methods, the structural properties of RNAs having randomly generated oligonucleotide sequences that were of sufficient length and information content to encode complex, functional folds, yet were unbiased by either genealogical or functional constraints. Typically, these unevolved, nonfunctional RNAs had sequence-specific secondary structure configurations and compact magnesium-dependent conformational states comparable to those of evolved RNA isolates. But unlike evolved sequences, arbitrary sequences were prone to having multiple competing conformations. Thus, for RNAs the size of small ribozymes, natural selection seems necessary to achieve uniquely folding sequences, but not to account for the well-ordered secondary structures and overall compactness observed in nature.

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Figure 1: PAGE of evolved and unevolved RNA sequences.
Figure 2: Velocity sedimentation results from evolved and unevolved RNA sequences.
Figure 3: Results of chemical probing of evolved and unevolved RNA sequences.

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Acknowledgements

We thank U. Müller, J.G. Ruby, M.S. Lawrence and J.S. Philo for comments on the manuscript; P. Hraber and M. Deras for computational assistance; V. Carey for statistical consultation; and R. Burton, G. Hersch and R. Sauer for use of the XL-A ultracentrifuge. This work was supported by grants from the US National Institutes of Health to D.P.B, from the Medical Foundation to E.A.S and from the US National Science Foundation to A.S. and U.M.

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Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, 02142, Massachusetts, USA

    Erik A Schultes & David P Bartel

  2. Boston College Department of Chemistry, Eugene F. Merkert Chemistry Center, 2609 Beacon Street, Chestnut Hill, 02467, Massachusetts, USA

    Alexander Spasic & Udayan Mohanty

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  1. Erik A Schultes
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Correspondence to David P Bartel.

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Supplementary information

Supplementary Fig. 1

Evolved and arbitrary RNA sequences (PDF 44 kb)

Supplementary Fig. 2

Mapping lead-induced cleavage coefficients onto known or predicted secondary structures for evolved and arbitrary RNA sequences (PDF 611 kb)

Supplementary Table 1

Estimated effective size and Stokes radii of folded RNAs (PDF 52 kb)

Supplementary Table 2

Sedimentation coefficients and fitted molecular masses (PDF 57 kb)

Supplementary Methods (PDF 185 kb)

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Schultes, E., Spasic, A., Mohanty, U. et al. Compact and ordered collapse of randomly generated RNA sequences. Nat Struct Mol Biol 12, 1130–1136 (2005). https://doi.org/10.1038/nsmb1014

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