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RNA enzymes with two small-molecule substrates

F Huang1, Z Yang, M Yarus

  • 1Department of Molecular, Cellular and Developmental Biology University of Colorado at Boulder Boulder CO 80309-0347, USA.

Chemistry & Biology
|November 30, 1998
PubMed
Summary
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RNA enzymes can join small molecules to form larger products, supporting the RNA world hypothesis. This ribozyme catalysis is independent of Watson-Crick base pairing, suggesting a complex ancestral metabolism.

Area of Science:

  • Origin of life studies
  • Biochemistry
  • Molecular evolution

Background:

  • The 'RNA world' hypothesis suggests early life used RNA for catalysis.
  • Modern RNA systems struggle with anabolic reactions involving non-base-pairing substrates.
  • This study investigates if this limitation is inherent or an artifact of selection methods.

Purpose of the Study:

  • To determine if RNA enzymes can catalyze anabolic reactions with non-base-pairing substrates.
  • To explore the catalytic capabilities of rationally designed ribozymes.

Main Methods:

  • Rational design and modification of RNA enzymes.
  • In vitro assays to test catalytic activity and substrate specificity.
  • Analysis of product formation and reaction rates.

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Main Results:

  • Three modified RNA enzymes (Iso6-G, Iso6-2G, Iso63G) were created.
  • Iso6-G RNA catalyzed the formation of polyphosphate-linked oligonucleotides.
  • This ribozyme exhibited substrate specificity for guanosine triphosphate and a non-specific site for small molecules, operating via multiple turnovers.

Conclusions:

  • Ribozymes can bind multiple small substrates and catalyze anabolic reactions independently of Watson-Crick base pairing.
  • These RNA enzymes mimic protein functions in overcoming entropic challenges for catalysis.
  • Findings support a complex RNA-catalyzed metabolism in early life.