Date of Award:

5-2012

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Chemistry and Biochemistry

Committee Chair(s)

Sean J. Johnson

Committee

Sean J. Johnson

Committee

Lance C. Seefeldt

Committee

Joan M. Hevel

Committee

Christopher P. Hill

Committee

Alvan C. Hengge

Abstract

To insure the integrity of nuclear RNA, the eukaryotic cell employs surveillance systems that identify and degrade RNAs that are detrimental or unneeded. The failure of RNA surveillance systems can lead to neurodegenerative disease states and cancer. The essential RNA helicase Mtr4 is required for the degradation and processing of several nuclear RNAs. To further the understanding of RNA surveillance and processing in eukaryotes, Ryan Jackson of the Department of Chemistry and Biochemistry at Utah State University has determined the molecular structure of Mtr4 and has used this structure to interrogate Mtr4 function biochemically. The structure revealed that Mtr4 contains a four domain helicase core, and a novel domain required for 5.8S ribosomal RNA processing. Furthermore, it was discovered that Mtr4 possesses a ratchet helix that contains conserved residues required for sensing specific substrate characteristics and unwinding activity. This five year, $300,000 project has significantly increased the understanding of Mtr4 structure and function and is currently being used as a platform for future studies aimed at dissecting the mechanisms of RNA surveillance.

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Comments

This work made publicly available electronically on December 21, 2012.

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