Ribozymes of the RNA World: Investigating Ancient Enzymes through Modern Self-Cleaving Ribozymes

Aamir Mir, Purdue University

Abstract

Ribozymes are RNAs that can perform catalytic functions. The discovery of ribozymes was an important milestone in science because it not only opened new avenues of research but also provided insights into the origins of life on Earth. Early life most likely used RNA as catalysts for diverse functions, however, it is unclear how RNA could have performed such diverse catalytic functions. To answer this question, my work has focused on the most abundant natural class of ribozymes in the modern world, called the self-cleaving ribozymes. They catalyze the cleavage of a specific phosphodiester bond in RNA. We investigated the different catalytic strategies used by one such ribozyme, called the hammerhead ribozyme, and uncovered how RNA can utilize tautomerization, divalent metals, and folding to diversify its chemical repertoire. To learn more about the catalytic strategies used by RNA and their biological roles, we developed a method that combines biochemistry of self-cleaving cleaving ribozymes with high-throughput sequencing to discover new self-cleaving ribozymes. New self-cleaving ribozymes will provide insights about their biological roles, and expand the catalytic toolkit available to RNA. Hence, by studying modern self-cleaving ribozymes, we can learn how ancient ribozymes catalyzed diverse chemical reactions, and the roles they may have played to sustain early life.

Degree

Ph.D.

Advisors

Golden, Purdue University.

Subject Area

Biology|Biochemistry|Biophysics

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