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Related Experiment Videos

Ribozyme-catalyzed aminoacylation from CoA thioesters.

Na Li1, Faqing Huang

  • 1Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, Mississippi 39406-5043, USA.

Biochemistry
|March 16, 2005
PubMed
Summary

Researchers discovered RNA enzymes (ribozymes) that link amino acids to Coenzyme A (CoA) thioesters. This finding suggests early RNA-based metabolic pathways and provides a potential ancestor for modern protein synthesis.

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RNA biology·2023

Area of Science:

  • Biochemistry
  • Origin of Life
  • RNA World Hypothesis

Background:

  • Coenzyme A (CoA) thioesters are crucial in contemporary metabolism.
  • The RNA World Hypothesis posits that RNA predated DNA and proteins as the primary genetic material and catalytic molecules.
  • Understanding early metabolic pathways is key to understanding the transition from an RNA world to the current DNA/protein-based system.

Purpose of the Study:

  • To investigate the potential biochemical functions of thioesters in an RNA-dominated world.
  • To identify ribozymes capable of catalyzing reactions involving Coenzyme A (CoA) thioesters.
  • To explore the evolutionary origins of aminoacylation systems, such as aminoacyl-tRNA synthetases.

Main Methods:

  • Isolation of a novel class of ribozymes (ACT) from a library of RNA molecules.

Related Experiment Videos

  • Assay development to measure the catalytic activity of isolated ribozymes in self-aminoacylation reactions.
  • Characterization of substrate requirements for active ribozymes, focusing on CoA thioester structure.

    • Main Results:

    • A new class of ribozymes (ACT) was isolated, catalyzing self-aminoacylation of Coenzyme A (CoA) thioesters.
    • Catalytic efficiencies for these ribozymes ranged from 7000 to 24,000 M⁻¹min⁻¹.
    • Active substrates require a free alpha-amino group on the acyl moiety and Coenzyme A (CoA) as the thiol component.

    Conclusions:

    • Ribozyme-catalyzed aminoacylation of CoA thioesters represents a plausible biochemical function in the RNA world.
    • These findings support the hypothesis that RNA-based aminoacylation systems could be ancestral to modern aminoacyl-tRNA synthetases.
    • An extensive RNA-catalyzed metabolic pathway involving CoA and its thioesters is proposed, potentially evolving into complex contemporary metabolic systems.