An RNA has been selected that rapidly aminoacylates its 2'(3') terminus when provided with phenylalanyl-adenosine monophosphate. That is, the RNA accelerates the same aminoacyl group transfer catalyzed by protein aminoacyl-transfer RNA synthetases. The best characterized RNA reaction requires both Mg2+ and Ca2+. These results confirm a necessary prediction of the RNA world hypothesis and represent efficient RNA reaction (> or = 10(5) times accelerated) at a carbonyl carbon, exemplifying a little explored type of RNA catalysis.
A 29-nt RNA catalyst successively forms the aminoacyl ester phe-RNA, and then peptidyl-RNA (phe-phe-RNA), given phenylalanine adenylate (phe-AMP) as substrate. Catalysis of two related reactions at similar rates supports the argument that RNA catalysts would evolve as groups with similar mechanisms. In particular, successive aminoacyl- and peptidyl-RNA synthesis by one RNA suggests that uncoded but RNA-catalyzed peptide synthesis would evolve before the synthesis of coded peptides.
RNA 77, derived by selection amplification, accelerates its own conversion to Phe-RNA (relative to randomized RNA) more than 6 ؋ 10 7 -fold, by using amino acid adenylates as substrate. A modified assay system allows measurement of slow rates of aa-RNA formation, which for disfavored amino acid substrates can be more than 10 4 -fold slower than phenylalanine. Thus unlike previously characterized self-aminoacylators, RNA 77 catalysis is highly amino acid selective. Remarkably, both rates of aminoacyl transfer and amino acid specificities are greater for RNA 77 than measured for protein PheRS. These data experimentally support the possible existence of an ancestral amino acidspecific translation system relying entirely on RNA catalysis. RNA 77 itself embodies a possible transitional evolutionary state, in which side-chain-specific aa-RNA formation and anticodon-codon pairing were invested in the same molecule.RNAs have been selected (1) that catalyze their own 2Ј(3Ј) aminoacylation by using amino acid adenylates as a substrate. Aminoacyl-adenylates (aa-AMPs) are the universal carboxyactivated precursors of modern aa-tRNAs. Because the products of RNA catalysis are (2Ј, 3Ј) aa-RNAs, chemically like aa-tRNAs, these RNA catalysts use biological precursors and make biological products, performing a reaction that parallels acylation of RNA by modern protein aa-tRNA synthetases. In addition, the current universality of adenylates and aa-RNAs suggests that they were used for translation by the last common ancestor of life on Earth. Thus self-aminoacylating RNAs also catalyze an essential translational reaction that has persisted at least since the last common ancestor.Self-aminoacylating RNAs also are ribozymes that perform carbonyl chemistry rather than the phosphoryl chemistry characteristic of natural ribozymes. This characteristic means that the tetrahedral, polar transition states characteristic of nucleophilic attack at carbonyl carbon are stabilized by RNAs, and that therefore other reactions with the same transition state (e.g., acyl transfers) are likely to be found. Examples of such reactions now include slight accelerations of aminoacyl ester hydrolysis (2) and amide hydrolysis (3, 4), which occur as apparent side reactions within derivatives of group I selfsplicing RNAs, as well as more rapid and specifically selected amide synthesis (5), aminoacyl ester transfer (6), and peptide formation (7). Such reactions are of more general evolutionary importance because ribosomal peptidyl transferase (8) is a related reaction.In one respect, previously characterized RNAs from the RNA 19-RNA 29 family, coselected sequences but of independent origin (9), are unlike protein aa-tRNA synthetases. Neither the originally selected 95-mer nor a small 43-nt active RNA (10) distinguish among amino acids in their substrates, giving acylation velocities of the same order whether supplied with Phe-AMP (used in the initial selection) or other aaAMPs. Lack of amino acid specificity would be a defect in a primordial RNA aa-RNA ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.