Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Biochemistry

Supervisor

Dr. Chris Brandl

Abstract

Tral is an essential yeast protein required for regulated transcription. Its human homolog TRRAP regulates factors important in oncogenesis. Mutation of leucine to alanine at position 3733 in the FATC domain {tralla) results in growth phenotypes including sensitivity to ethanol. My aim was to examine genetic interactions o f the FA TC domain o f Tral to define its cellular role. I screened for extragenic suppressors of the ethanol sensitivity caused by tralla, identifying an opal mutation at tryptophan 165 of NAM7 as a suppressor. Deleting nam7, upf3, or nmd2 similarly suppressed tralLA, thereby linking Tral to nonsense mediated decay. I propose that Tral regulates transcription of genes also regulated by NMD. This work emphasizes the importance of NMD in gene regulation. Furthermore, the cross regulation between Tral and NMD suggests that mutations in the human NMD machinery may provide a mechanism to alter pathways influenced by TRRAP in human disease.

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