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RIBOZYME

A ribozyme (from ribonucleic acid enzyme, also called RNA enzyme or catalytic RNA) is an RNA molecule that catalyzes a chemical reaction. Many natural ribozymes catalyze either their own cleavage or the cleavage of other RNAs, but they have also been found to catalyze the aminotransferase activity of the ribosome. Investigators studying the origin of life have produced ribozymes in the laboratory that are capable of catalyzing their own synthesis under very specific conditions.

Contents

Discovery

Before the discovery of ribozymes, proteins were the only known biological catalysts. In 1967, Carl Woese, Francis Crick, and Leslie Orgel were the first to suggest that RNA could act as a catalyst based upon findings that it can form complex secondary structures[1]. The first ribozymes were discovered in the 1980s by Thomas R. Cech, who was studying RNA splicing in the ciliated protozoan Tetrahymena thermophila and Sidney Altman, who was working on the bacterial RNase P complex. The ribozymes were found in the intron of an RNA transcript, which removed itself from the transcript and in the RNA component of the RNase P complex, which is involved in the maturation of pre-tRNAs. In 1989, Thomas R. Cech and Sidney Altman won the Nobel Prize in chemistry for their "discovery of catalytic properties of RNA."[2]


Activity

Although most ribozymes are quite rare in the cell, their roles are sometimes essential to life. For example, the functional part of the ribosome, the molecular machine that translates RNA into proteins, is fundamentally a ribozyme. Ribozymes often have divalent metal ions such as Mg2+ as cofactors.

RNA can also act as a hereditary molecule, which encouraged Walter Gilbert to propose that in the past, the cell used RNA as both the genetic material and the structural and catalytic molecule, rather than dividing these functions between DNA and protein as they are today. This hypothesis became known as the "RNA world hypothesis" of the origin of life.

If ribozymes were the first molecular machines used by early life, then today's remaining ribozymes -- such as the ribosome machinery -- could be considered living fossils of a life based primarily on nucleic acids.

A recent test-tube study of prion folding suggests that an RNA may catalyze the pathological protein conformation in the manner of a chaperone enzyme[3].

Some known ribozymes include RNase P, Group I and Group II introns, leadzyme, hairpin ribozyme, hammerhead ribozyme, hepatitis delta virus ribozyme, and tetrahymena ribozyme.

Synthetic Ribozymes

Since the discovery of ribozymes that exist in living organisms, there has been interest in the study of new synthetic ribozymes made in the laboratory. For example, artificially-produced self-cleaving RNAs that have good enzymatic activity have been produced. Tang and Breaker [4] isolated self-cleaving RNAs by in vitro selection of RNAs originating from random-sequence RNAs. Some of the synthetic ribozymes that were produced had novel structures, while some were similar to the naturally occurring hammerhead ribozyme.

References

  1. ^ Carl Woese, The Genetic Code (New York: Harper and Row, 1967).
  2. ^ The Nobel Prize in Chemistry 1989 was awarded to Thomas R. Cech and Sidney Altman "for their discovery of catalytic properties of RNA".
  3. ^ "Prion protein conversion in vitro" by S. Supattapone (2004) in Journal of Molecular Medicine Volume 82, pages 348-356. Entrez PubMed 15014886

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