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LET'S TALK LIFE SCIENCE MOLECULAR BIOLOGY

Suraj Prakash Sharma | Ekta Chotia

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4.10.      Ribozymes

RNA used as catalysts in living cells, other than their known roles in information storage and as molecular architectural frameworks are called ribozymes. This idea was so profoundly contrary to the central dogma of molecular biology that it resulted in the award of a Nobel Prize to two of the early proponents, Thomas Cech and Sidney Altman. The discovery was twofold – RNA segments that cut themselves out of larger RNAs (self-splicing introns) and a protein-assisted RNA enzyme (ribonuclease P) that cuts the leader sequences off all transfer RNAs throughout the three organismal domains. RNAs with catalytic activity, revealed the extraordinary characteristic of this molecule, and collaborated the idea that RNA was the first informative polymer. The catalytic properties of ribozymes are majorly due to the capacity of RNA molecules to fold into particular structures. The versatile structures of RNA can allow a single RNA sequence to fold in more than one structure providing them with the virtue of multiple functions.

Ribozymes are found in nucleus, mitochondria and chloroplasts of eukaryotes, as well as in some viruses. These are grouped by their chemical type, but regardless of the type, all RNA are associated with metal ions such as potassium (K+) or magnesium (Mg2+), which play essential roles in catalyzing reactions.

Most ribozymes are involved in the processing of RNA. They either serve as “molecular scissors” or as “staplers” that cleave and ligate  molecules of RNA. Although most targets of ribozymes are RNA, evidence suggests that the assembly of amino acids into a protein that occurs during translation is also catalyzed by RNA, meaning the ribosomal RNA is also a ribozyme.

Group II introns are autocatalytic ribozymes that catalyze RNA splicing and retrotransposition. Splicing by group II introns plays an essential role in the metabolism of plants, fungi, and yeast and contributes to genetic variation in many bacteria. Group II introns are also responsible for genome evolution. The structure and catalytic mechanism of group II introns have been elucidated through a combination of genetics, chemical biology, biochemistry, and crystallography. A central active site, containing a reactive metal ion, catalyzes both steps of self-splicing. These studies provide insights into RNA structure, folding, and catalysis, as they raise new questions for the behavior of RNA machines.

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