How many catalytic RNAs? Ions and the Cheshire cat conjecture

  title={How many catalytic RNAs? Ions and the Cheshire cat conjecture},
  author={Michael Yarus},
  journal={The FASEB Journal},
  pages={31 - 39}
  • M. Yarus
  • Published 1 January 1993
  • Chemistry, Biology
  • The FASEB Journal
Three well‐characterized RNA catalysts not only require Mg2+ for activity, but also bind a metal ion (or ions) within the active site, apparently in a catalytic rather than solely structural role. I suggest, in view of the general catalytic utility of bound ions, that catalytic RNAs be viewed as Cheshire cats, by dimming their complex three‐dimensional ribonucleotide structure to leave only the sharp mineral parts in view. That is, catalytic RNAs may be viewed as metalloenzymes, with the… 

An amino acid as a cofactor for a catalytic polynucleotide.

  • A. RothR. Breaker
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
Kinetic analysis indicates that a DNA-histidine complex may perform a reaction that is analogous to the first step of the proposed catalytic mechanism of RNase A, in which the imidazole group of histidine serves as a general base catalyst.

Mechanistic aspects of enzymatic catalysis: lessons from comparison of RNA and protein enzymes.

The aim of comparing RNA and protein enzymes is to learn about fundamental physical and chemical principles of biological catalysis, and the differences described in this review have taught us about the aspects of RNA and proteins that are distinct, whereas the common features have helped to understand the aspects that are fundamental to biologicalCatalysis.

Emergence of a dual-catalytic RNA with metal-specific cleavage and ligase activities: the spandrels of RNA evolution.

In vitro evolution is used to select a ribozyme that catalyzes a novel template-directed RNA ligation that requires surprisingly few nucleotides for catalytic activity, implying that similar catalytic RNA motifs can arise under fairly simple conditions and that multiple catalytic structures, including bifunctional ligases, can evolve from very small preexisting parts.

Dynamic evidence for metal ion catalysis in the reaction mediated by a flap endonuclease

The role of metal ion cofactors in phosphate diester hydrolysis catalysed by a flap endonuclease has been studied and the kinetic pKas display good correlation with the acidity of the corresponding hexahydrated metal ions, which strongly suggests a role for metal‐bound hydroxide, or its equivalent ionic species, in the reaction.

Unwinding the twister ribozyme: from structure to mechanism

Evidence for innersphere coordination of a Mg2+ ion to the pro‐S nonbridging oxygen of the scissile phosphate stems from two of the four crystal structures suggests the participation of divalent ions in the overall catalytic strategy employed by twister ribozymes.

Relics from the RNA World

The model as developed serves as an outgroup to root the tree of life and is an alternative to using sequence data for inferring properties of the earliest cells.

Structure and function of the hairpin ribozyme.

  • M. Fedor
  • Biology, Chemistry
    Journal of molecular biology
  • 2000
The hairpin ribozyme is a better ligase than it is a nuclease while the hammerhead reaction favors cleavage over ligation of bound products by nearly 200-fold, and structure-function studies have begun to yield insights into the molecular bases of these unique features of the hairpin Ribozyme.

Structure-function relationships in RNA and RNP enzymes: recent advances.

The structural biology of ribozymes and ribonucleoprotein (RNP) enzymes is now sufficiently advanced that a true dialogue between structural and functional studies is possible. In this review, we



Metal ion catalysis in the Tetrahymena ribozyme reaction

It is concluded that the Tetrahymena ribozyme is a metalloenzyme, with mechanistic similarities to several protein enzymes9–12, and contributes directly to catalysis by coordination to the 3′ oxygen atom in the transition state, presumably stabilizing the developing negative charge on the leaving group.

Metal ion requirements for sequence-specific endoribonuclease activity of the Tetrahymena ribozyme.

It is postulated that two classes of metal ion binding sites are required for catalysis, with Mg2+ and Mn2+ being the only metal ions that by themselves give RNA enzyme activity.

A crystallographic study of metal-binding to yeast phenylalanine transfer RNA.

Mixed deoxyribo- and ribo-oligonucleotides with catalytic activity

Structurally less-disrupted hammerhead analogues in which deoxyribon nucleotides, which lack 2′-OH groups, are substituted for ribonucleotides are constructed, indicating that the three-dimensional struc-ture producing nucleic acid-type catalysis is not restricted to RNA.

Dissecting the catalytic triad of a serine protease

Kinetic analyses of the multiple mutants demonstrate that the residues within the triad interact synergistically to accelerate amide bond hydrolysis by a factor of ∼2×l06, which is in contrast to the effect of mutations in residues involved in substrate binding.

Catalytic RNA and RNA Splicing

The removal of introns from nuclear pre-messenger RNA (pre-mRNA) shares fundamental properties with certain RNA self-splicing reactions, and it seems likely that the small nuclear RNAs (snRNAs) are carried out by the small ribonucleoprotein (RNP) complex in the cell nucleus, called the spliceosome.

Influence of metal ions on the ribonuclease P reaction. Distinguishing substrate binding from catalysis.

Metal coordination sites that contribute to structure and catalysis in the group I intron from Tetrahymena.

Roles for the corresponding ions in stabilizing tertiary structure and substrate recognition and as participants in catalysis are suggested by the direct coordination of divalent metal ions within the highly conserved catalytic core of the Tetrahymena intron.

In vitro selection of RNAs that undergo autolytic cleavage with Pb2+.

Both specific mutations and terminal truncation experiments suggest that the D and T loops of these two variants interact in a manner similar to that of tRNA(Phe) despite the absence of the G18U55 and G19C56 tertiary interactions.

Structural studies on the active site of Escherichia coli RNA polymerase. 2. Geometrical relationship of the interacting substrates.

A model has been constructed for the geometry of interaction of two ATP molecules poised on the active site of the Escherichia coli enzyme for the formation of the first bond in RNA synthesis.