Peptide bond formation by in vitro selected ribozymes

  title={Peptide bond formation by in vitro selected ribozymes},
  author={Biliang Zhang and Thomas R. Cech},
An attractive solution to the problem of the origin of protein synthesis in an evolving ‘RNA world’ involves catalysis by nucleic acid without assistance from proteins,. Indeed, even the modern ribosome has been considered to be fundamentally an RNA machine, and the large ribosomal subunit can carry out peptidyl transfer in the absence of most of its protein subunits. Successive cycles of in vitro selection and amplification have been used to find RNAs that perform many biochemical reactions… 

A novel ribozyme with ester transferase activity.

Peptidyltransfer Reaction Catalyzed by the Ribosome and the Ribozyme: a Dissertation

The newly established assay for ribosomal peptidyltransferase reaction provides a good system to investigate the mechanism of ribosome reaction and may have potential application in drug screening to search for the specific peptidoltransferase inhibitors.

Oligonucleotide-directed peptide synthesis in a ribosome- and ribozyme-free system.

  • K. TamuraP. Schimmel
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
Peptide bond formation can be achieved without the ribosome or rRNA simply by using a piece of tRNA mixed with sequence-specific oligonucleotides that contained puromycin, and imidazole as a catalyst was required.

Arginine Cofactors on the Polymerase Ribozyme

Results suggest that the existing polymerase ribozyme is not well suited to using an arginine cofactor, because this is the amino acid most adept to interact with RNA.

Toward Ribosomal RNA Catalytic Activity in the Absence of Protein

The ease with which alternate catalytic activity was selected from rRNA with a small number of mutations suggests that rRNA may have inherent activity, and represents a step on the path toward isolating that native activity.

Ribozyme-catalyzed tRNA aminoacylation

It is reported here that a bifunctional ribozyme generated by directed in vitro evolution can specifically recognize an activated glutaminyl ester and aminoacylate a targeted tRNA, via a covalent aminoacyl-ribozyme intermediate.

A ribozyme for the aldol reaction.

Ala-His Mediated Peptide Bond Formation Revisited

A product is produced which can be readily mistaken for a dipeptide in the TLC separation systems employed in earlier work and is consistent with the notion that the translation machinery was likely based on catalytic RNA from its very inception.



Ribozyme-catalysed amino-acid transfer reactions

In vitro selection and evolution is used to isolate ribozymes with acyl transferase activity from a pool of random RNA sequences and one of them transfers an amino acid to itself in a reaction that is analogous to peptidyl transfer on the ribosome.

In vitro evolution of a self-alkylatlng ribozyme

RNA enzymes are postulated to have catalysed all chemical reactions in the earliest living cells, and selection for self-biotinylation yields a transfer RNA-like ribozyme that efficiently catalyses carbon–nitrogen bond formation.

Aminoacyl esterase activity of the Tetrahymena ribozyme.

The ability of RNA to catalyze reactions with aminoacyl esters expands the catalytic versatility of RNA and suggests that the first aminoacyL tRNA synthetase could have been an RNA molecule.

Cleavage of an amide bond by a ribozyme

A variant form of a group I ribozyme, optimized by in vitro evolution for its ability to catalyze magnesium-dependent phosphoester transfer reactions involving DNA substrates, also catalyzes the

Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA

The selected molecule represents the discovery of the first RNA enzyme known to cleave single-stranded DNA specifically and allows evolution experiments to be carried out in response to artificially imposed selection constraints.

Isolation of new ribozymes from a large pool of random sequences [see comment].

An iterative in vitro selection procedure was used to isolate a new class of catalytic RNAs (ribozymes) from a large pool of random-sequence RNA molecules, leading to improvement of the average ligation activity and the emergence of ribozymes with reaction rates 7 million times faster than the uncatalyzed reaction rate.

In vitro selection of a novel catalytic RNA: characterization of a sulfur alkylation reaction and interaction with a small peptide.

An in vitro RNA selection for catalytic activity was used to co-select for binding activity to a small peptide, showing that the intrinsic reactivity of the 5' phosphorothioate is not increased in the selected RNA.

RNA-catalysed RNA polymerization using nucleoside triphosphates

An RNA is described that synthesizes RNA using the same reaction as that employed by protein enzymes that catalyse RNA polymerization, and shows marked template fidelity.

Aminoacyl-RNA synthesis catalyzed by an RNA

An RNA has been selected that rapidly aminoacylates its 2'(3') terminus when provided with phenylalanyl-adenosine monophosphate and this results confirm a necessary prediction of the RNA world hypothesis and represent efficient RNA reaction at a carbonyl carbon.

Expanding the scope of RNA catalysis.

The basic notions of transition state theory have been exploited in the past to generate highly selective catalysts from the vast library of antibody molecules in the immune system. These same ideas