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Related Experiment Videos

New catalytic structures from an existing ribozyme.

Edward A Curtis1, David P Bartel

  • 1Whitehead Institute for Biomedical Research and Department of Biology, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.

Nature Structural & Molecular Biology
|October 18, 2005
PubMed
Summary
This summary is machine-generated.

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New ribozymes with novel functions and structures can emerge from existing RNA scaffolds. Escaping the original fold significantly increases the likelihood of discovering these new ribozymes.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • RNA Catalysis

Background:

  • Protein enzymes can evolve new functions from existing structures.
  • Mechanisms for the origin of new macromolecular folds in proteins and RNA are poorly understood.
  • Ribozymes, RNA molecules with catalytic activity, offer a model for studying the evolution of molecular function and structure.

Purpose of the Study:

  • To investigate the ease with which new catalytic activities and folds can arise from an existing ribozyme scaffold.
  • To explore the relationship between mutational distance and the emergence of novel ribozyme functions and folds.

Main Methods:

  • In vitro selection was employed to screen a large library of ribozyme variants.
  • A parent aminoacylase ribozyme was used as the starting scaffold.

Related Experiment Videos

  • Sequence variants were selected for new kinase activity.

    • Main Results:

    • Twenty-three distinct kinase ribozymes were successfully isolated from the selected variants.
    • Ribozymes with novel folds and biochemical activities were found relatively close to the parent ribozyme in sequence space.
    • The probability of isolating new ribozymes increased significantly with greater mutational distance from the parental scaffold.

    Conclusions:

    • New ribozyme folds and catalytic activities can readily emerge from existing ribozyme scaffolds.
    • Significant evolutionary distance from the parent ribozyme is beneficial for discovering novel ribozyme functions and structures.
    • These findings provide insights into the evolutionary potential of RNA and the mechanisms of macromolecular innovation.