Title

The Role of RNA and Iron-Sulfur Clusters in the Biosynthesis of Deoxyribonucleotides. Haley D. Hill & Jason Willis

Document Type

Article

Publication Date

2004

Abstract

For years scientists have relentlessly searched for the origin of life on earth. Though many theories have been proposed most have been refuted through experimentation. One theory active today, is known as the "RNA World Hypothesis". According to the "RNA World Hypothesis", in the prebiotic milieu RNA superceded both DNA and proteins. This theory is based on the knowledge that RNA has a limited catalytic function and is capable of carrying genetic code, thus incorporating the functions of DNA and proteins. The data about RNA?s capabilities coupled with the idea that RNA could have catalyzed the reduction of ribose to deoxyribose in the primordial soup is a tantalizing proposition. At present DNA is produced in cells by protein enzymes, but DNA which is used as a template controls the synthesis of those proteins. If this is known to be the case, how did DNA first from? Our laboratory has proposed that RNA-based enzymes (ribozymes) catalyzed the early synthesis of DNA nucleotides without the use of proteins. We have begun to investigate this possibility using in vitro RNA selection techniques and have developed a sensitive chemical assay for enzymatic activity. Here we turn our attention toward incorporating transition metal cofactors into our synthetic ribozymes in an effort to enhance their catalytic activity. Iron and sulfur are theorized to have been prevalent in the primordial soup, and self-assemble into redox-active iron-sulfur clusters in proteins. By analogy, RNA?s that are capable of binding iron sulfur clusters may be discovered that can harness this cofactor to enhance RNA?s catalytic activity. These studies will provide insight into the possible existence of a metal-binding RNA molecules capable of generating the basic building blocks of DNA, and may provide a link between the ancient RNA world and modern living organisms.

Advisor

W. R. Hardy, J. Franck, and M. G. Hill

Department

chem

Support

Support provided by:Beckman Scholars Award and Camille and Henry Dreyfus Foundation Grant

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