Screening for Primordial RNA-Peptide Interactions Using High-Density Peptide Arrays

Area of Science:

• Biochemistry
• Molecular Biology
• Origin of Life Studies

Background:

• RNA-peptide interactions are fundamental to translation and the genetic code's evolution.
• Existing bioinformatics approaches lack experimental methods to detail individual amino acid contributions to RNA-peptide bonds.
• Progress in RNA-protein complex data necessitates new experimental strategies.

Purpose of the Study:

• To experimentally determine the influence of individual amino acids on non-covalent RNA-peptide interactions.
• To investigate the binding affinity of primordial peptides to homo-oligonucleotides.
• To evaluate the impact of peptide length and composition on RNA binding strength.

Main Methods:

• Design of combinatorial peptide libraries using Watson-Crick mutation-based fusion rules.
• High-density peptide arrays for probing interactions with cognate homo-oligonucleotides.
• Calculation of interaction scores for peptide fragments and assessment of binding strength.

Main Results:

• Identified phenylalanine, tyrosine, and proline as key amino acids promoting strong RNA-peptide binding.
• Demonstrated that the overall charge of a peptide does not significantly affect RNA binding.
• Quantified the contribution of peptide length and amino acid composition to binding affinity.

Conclusions:

• Specific amino acids play a critical role in the strength of RNA-peptide interactions.
• The findings support the combinatorial fusion cascade hypothesis regarding amino acid partitioning.
• Provides a foundation for understanding early molecular evolution and the genetic code.