Structure and Function

The RNA catalysts called ribozymes are found in the nucleus, mitochondria, and chloroplasts of eukaryotic organisms. Some viruses, including several bacterial viruses, also have ribozymes. The ribozymes discovered to date can be grouped into different chemical types, but in all cases the RNA is associated with metal ions, such as magnesium (Mg2+) or potassium (K+), that play important roles during the catalysis. Almost all ribozymes are involved in processing RNA. They act either as molecular scissors to cleave precursor RNA chains (the chains that form the basis of a new RNA chain) or as "molecular staplers" that ligate two RNA molecules together. Although most ribozyme targets are RNA, there is now very strong evidence that the linkage of amino acids into proteins, which occurs at the ribosome during translation, is also catalyzed by RNA. Thus, the riboso-mal RNA is itself also a ribozyme.

In some ribozyme-catalyzed reactions, the RNA cleavage and ligation processes are linked. In this case, an RNA chain is cleaved in two places and the middle piece (called the intron) is discarded, while the two flanking RNA pieces (called exons) are ligated together. This reaction is called splicing. Besides ribozyme-mediated splicing, which involves RNA alone, there are some splicing reactions that involve RNA-protein complexes. These complexes are called small nucleus ribonucleoprotein particles, abbreviated as snRNPs. This class of splicing is a very common feature of messenger RNA (mRNA) processing in "higher" eukaryotes such as humans. It is not yet known if snRNP-mediated splicing is catalyzed by the RNA components. Note also that some RNA splicing reactions are catalyzed by enzymes made of only protein.

Some precursor RNA molecules have a ribozyme built into their own intron, and this ribozyme is responsible for removal of the intron in which it is found. These are called self-splicing RNAs. After the splicing reaction is complete, the intron, including the ribozyme, is degraded. In these cases, each ribozyme works only once, unlike protein enzymes that catalyze a reaction repeatedly. Examples of self-spliced RNAs include the ribosomal RNAs of ciliated protozoa and certain mRNAs of yeast mitochondria.

Some RNA viruses, such as the hepatitis delta virus, also include a ribozyme as part of their inherited RNA molecule. During replication of the viral RNA, long strands containing repeats of the RNA genome (viral genetic information) are synthesized. The ribozyme then cleaves the long multimeric molecules into pieces that contain one genome copy, and fits that RNA piece into a virus particle.

Other ribozymes work on other RNA molecules. One ribozyme of this type is RNase P, which consists of one RNA chain and one or more proteins (depending on the organism). The catalytic mechanism of RNase P has been especially well-studied in bacteria. This ribozyme processes precursor transfer RNA (tRNA) by removing an extension from the 5-prime end, to create the 5-prime end of the "mature" tRNA (the two ends of an RNA molecule are chemically distinct and are called the 5-prime and 3-prime ends, referring to specific carbons in the sugar moiety of the terminal nucleotides). When the RNA molecule from bacterial RNase P is purified away from its protein, it can still cleave its precursor tRNA target, albeit at a very slow rate, proving that the RNA is the catalyst. Nevertheless, the protein(s) in RNase P also has important functions, such as maintenance of the proper conformation of the RNase P RNA and interaction with the precursor tRNA.

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