title: Peptide-templated nucleic acid ligation.
abstract: Short oligonucleotide and peptide replicators have been described. To determine whether cross-replication could have occurred between such systems, we have attempted to show that peptides can specifically template the ligation of nucleic acids. A complex between a 35-mer anti-Rev RNA aptamer and a 17-mer arginine-rich motif (ARM) peptide from the HIV-1 Rev protein served as a model system. Aptamer half-molecules were activated for ligation via two activation chemistries, representing two distinct kinetic possibilities for early replicators. Cyanogen bromide activation was transient relative to oligonucleotides that terminated with a 5'-iodine and a 3'phosphorothioate, respectively. The Rev ARM specifically enhanced the degree or rate of ligation by both methods: there was a 10-fold increase in the production of full-length aptamer in the presence of cyanogen bromide and a 5.9- to 7.6-fold enhancement in the rate of ligation for stably activated aptamer half-molecules. These results support the possibility that life could have originated with peptide replicators and transitioned to nucleic acid replicators or that peptide and nucleic acid replicators could have been interdependent.
authors.affiliation: Department of Chemistry and Biochemistry, Institute for Cell and Molecular Biology, University of Texas at Austin, 78712, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Levy
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Ellington
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003488:Cyanogen Bromide / Q000737:chemistry; D019143:Evolution, Molecular; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis* / Q000737:chemistry; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D013698:Templates, Genetic; D015533:Transcriptional Activation
chemical_list: C119724:AGFG1 protein, human; D015696:Gene Products, tat; C099695:MANF protein, human; D009414:Nerve Growth Factors; D028861:Nuclear Pore Complex Proteins; D020135:Peptide Nucleic Acids; D010455:Peptides; D011506:Proteins; D016601:RNA-Binding Proteins; D012313:RNA; D003488:Cyanogen Bromide