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Compact and ordered collapse of randomly generated RNA sequences

Nature Structural & Molecular Biology volume 12, pages 11301136 (2005) | Download Citation

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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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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.

Author information

Affiliations

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

    • Erik A Schultes
    •  & David P Bartel
  2. Boston College Department of Chemistry, Eugene F. Merkert Chemistry Center, 2609 Beacon Street, Chestnut Hill, Massachusetts 02467, USA.

    • Alexander Spasic
    •  & Udayan Mohanty

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David P Bartel.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Evolved and arbitrary RNA sequences

  2. 2.

    Supplementary Fig. 2

    Mapping lead-induced cleavage coefficients onto known or predicted secondary structures for evolved and arbitrary RNA sequences

  3. 3.

    Supplementary Table 1

    Estimated effective size and Stokes radii of folded RNAs

  4. 4.

    Supplementary Table 2

    Sedimentation coefficients and fitted molecular masses

  5. 5.

    Supplementary Methods

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DOI

https://doi.org/10.1038/nsmb1014

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