The chemical repertoire of natural ribozymes

  title={The chemical repertoire of natural ribozymes},
  author={Jennifer A. Doudna and Thomas R. Cech},
Although RNA is generally thought to be a passive genetic blueprint, some RNA molecules, called ribozymes, have intrinsic enzyme-like activity — they can catalyse chemical reactions in the complete absence of protein cofactors. In addition to the well-known small ribozymes that cleave phosphodiester bonds, we now know that RNA catalysts probably effect a number of key cellular reactions. This versatility has lent credence to the idea that RNA molecules may have been central to the early stages… 

The chemical versatility of RNA

  • D. A. HillerS. Strobel
  • Biology, Chemistry
    Philosophical Transactions of the Royal Society B: Biological Sciences
  • 2011
Observations indicate RNA is a versatile molecule that could, in principle, catalyse the myriad reactions necessary to sustain life.

Selection in vitro of allosteric ribozymes.

This chapter describes a procedure known as allosteric selection, in which an RNA catalyst in conjunction with a random sequence domain is subjected to iterative in vitro selection in order selectively to recover ligand-dependent ribozymes.

Ribozyme-Catalyzed Genetics

Challenges include increasing the vigor with which the individual reactions are catalyzed, strengthening the affinity and specificity of substrate recognition, integrating ribozymes into metabolic paths and coordinated networks of linked reactions, and derived a ribozyme-catalyzed metabolic context to sustain the core reactions.

Two decades of RNA catalysis.

  • V. DeRose
  • Biology, Chemistry
    Chemistry & biology
  • 2002

ReviewTwo Decades of RNA Catalysis

Biological repertoire of these enzymes was expanded on the current state of proposed mechanisms for four recently as a result of new evidence suggesting that ribozymes that have been the subject of particularly the RNA component of the ribosome catalyzes peptide extensive investigations.

A ribozyme for the aldol reaction.

Engineered Ribozymes as Molecular Tools for Site‐Specific Alteration of RNA Sequence

  • S. Müller
  • Biology
    Chembiochem : a European journal of chemical biology
  • 2003
Over the past decade, four major approaches have emerged to modulate gene function at the RNA level: trans-splicing by group I intron ribozymes, trans-Splicing mediated by the spliceosome, use of antisense oligonucleotides to modify splicing pathways, and antisense aggregates that are capable of activating the cellular enzyme double-stranded RNA adenosine deaminase (ADA).

Ribozymes and Deoxyribozymes Switched by Oligonucleotides

A remarkable variety of approaches that have been used to generate ribozymes and deoxyribozymes that can be switched on (and, occasionally, off) by specific RNA or DNA oligonucleotides are reviewed.



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.

The hairpin ribozyme: structure, assembly and catalysis

  • WalterBurke
  • Chemistry, Biology
    Current opinion in chemical biology
  • 1998

Selection of RNA amide synthases.

Rational design of allosteric ribozymes.

Rearrangement of a stable RNA secondary structure during VS ribozyme catalysis.

Capturing the Structure of a Catalytic RNA Intermediate: The Hammerhead Ribozyme

The crystal structure of an unmodified hammerhead RNA in the absence of divalent metal ions has been solved, and it was shown that this ribozyme can cleave itself in the crystal when divalent metal

The question remains: Is the spliceosome a ribozyme?

Data is reviewed consistent with the hypothesis that Prp8 functions as a cofactor to an RNA enzyme in the catalytic core of the large ribonuclear protein machine called the spliceosome.

Maximizing RNA folding rates: a balancing act.

This work proposes that folding rates are maximized when the free energies of forming independent domains are similar to each other, and predicts that the folding pathway of the ribozyme can be reversed by inverting the relative stability of the tertiary domains.

Novel RNA catalysts for the Michael reaction.