Date of Award:

5-2016

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Chemistry and Biochemistry

Committee Chair(s)

Sean J. Johnson

Committee

Sean J. Johnson

Committee

Joan M. Hevel

Committee

Nicholas E. Dickenson

Abstract

Cells function through a variety of regulatory pathways intricately communicating with one another. These pathways ensure that cellular functions happen at the appropriate times and keep the natural balance within the cell. When pathways do not communicate appropriately, this can lead to disease states and cell death. Two such connected pathways in Neurospora crassa involve the regulation of RNA levels and the circadian rhythms essential for these cells to maintain homeostasis. These pathways are connected by a unique helicase called the Frequency-interacting RNA Helicase (FRH), named for its discovery with the frequency protein involved in the circadian oscillation of the fungus, N. crassa. All eukaryotes require a way to maintain RNA levels within the cell, in eukaryotes the majority of RNA is processed or degraded by the exosome and associated proteins. The exosome requires an RNA helicase from the family of Ski2-like helicases to function. In N. crassa this Ski-2 like helicase is FRH. Other RNA helicases have been studied, especially in yeast with the similar protein Mtr4 that is also involved in RNA surveillance. Due to this similarity it is predicted that FRH has a similar structure and function to Mtr4. However, no other RNA helicase has been shown to be incorporated in the separate regulation of circadian rhythms. The role of FRH in Neurospora is intriguing and provides a unique system to study both RNA surveillance and circadian oscillation. Here we present a structural and biochemical characterization of FRH which is similar to the yeast Mtr4 yet forms a unique dimer not previously observed. Discussion for the biological relevance of the FRH dimer is presented and future work proposed.

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