Assembly of catalytic complexes from randomized oligonucleotides.

Area of Science:

• Origin of life studies
• Biochemistry
• Molecular evolution

Background:

• Early life's functions depended on catalytic RNAs, known as ribozymes.
• The assembly of these early catalysts from simpler components in primordial environments is a key question in origin of life research.

Purpose of the Study:

• To investigate if catalytic RNAs could assemble from multiple short nucleic acid fragments in random sequence environments.
• To determine if DNA oligomers could act as essential cofactors for early RNA catalysts.

Main Methods:

• In vitro selection experiments using a short RNA library and 256 different DNA 20-nucleotide oligomers.
• High-throughput sequencing to analyze selected RNA sequences.
• Biochemical assays to confirm catalytic activity and cofactor requirements.

Main Results:

• Most selected RNA sequences (1331 total) required at least one DNA cofactor for activity.
• Four distinct clusters of RNA sequences showed catalytic activity dependent on DNA cofactors.
• These DNA-dependent RNA catalysts remained active when DNA cofactors were randomly generated, indicating robust cofactor recruitment.

Conclusions:

• Catalytic RNA-DNA complexes can form and function even with random DNA sequences, suggesting a plausible mechanism for early catalyst evolution.
• The recruitment of oligonucleotide cofactors from random libraries is a significant principle for the emergence of the earliest oligonucleotide catalysts.
• This research provides insights into how complex catalytic functions may have arisen from simple nucleic acid precursors in prebiotic environments.