title: The plausibility of RNA-templated peptides: simultaneous RNA affinity for adjacent peptide side chains.
abstract: According to the RNA world hypothesis, coded peptide synthesis (translation) must have been first catalyzed by RNAs. Here, we show that small RNA sequences can simultaneously bind the dissimilar amino acids His and Phe in peptide linkage. We used in vitro counterselection/selection to isolate a pool of RNAs that bind the dipeptide NH(2)-His-Phe-COOH with K (D) ranging from 36 to 480 μM. These sites contact both side chains, usually including the protonated imidazole of His, but bind-free L: -His and L: -Phe with much lower, sometimes undetectable, affinities. The most frequent His-Phe sites do not usually contain previously isolated sites for individual amino acids, and are only ≈35 % larger than previously known separate His and Phe sites. Nonetheless, His-Phe sites appear enriched in His anticodons, as previous L: -His sites also were. Accordingly, these data add to existing experimental evidence for a stereochemical genetic code. In these peptide sites, bound amino acids approach each other to a proximity that allows a covalent peptide linkage. Isolation of several RNAs embracing two amino acids with a linking peptide bond supports the idea that a direct-RNA-template could encode primordial peptides, though crucial experiments remain.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Turk-Macleod
authors.forename: Deepa
authors.initials: D
authors.lastname: Puthenvedu
authors.forename: Irene
authors.initials: I
authors.lastname: Majerfeld
authors.forename: Michael
authors.initials: M
authors.lastname: Yarus
mesh_terms: D000926:Anticodon; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism*; D019143:Evolution, Molecular; D006639:Histidine / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D000926:Anticodon; D052157:Aptamers, Nucleotide; D004151:Dipeptides; C022144:histidylphenylalanine; D010649:Phenylalanine; D006639:Histidine; D012313:RNA