Date of Award

Winter 12-15-2017

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Regulation of gene expression is essential for cellular development and survival. The great variety and complexity of regulatory mechanisms underscores this fact. Messenger RNA stability and translational efficiency are often key determinants of gene expression. mRNA surveillance pathways, discovered for their role in degradation of aberrant mRNA, are now known to be instrumental in the regulation of physiologically correct mRNA stability. Thus, the study of cis elements in a transcript that can induce mRNA surveillance pathways has become an area of particular interest.

Here I report on the mechanism of gene regulation by coding polyA tracks, defined as a sequence of at least 12 consecutive nucleotides in which all but one are adenosines. When a polyA track is present in the open reading frame of an mRNA, the translating ribosome stalls and frameshifts due to interactions with the polyA sequence. These events lead to degradation of the transcripts by the mRNA surveillance pathways no-go decay and nonsense mediated decay. As a consequence of the polyA sequence, less protein is expressed from these transcripts. Approximately 2% of genes in most genomes, including humans, contain a polyA track and are potentially regulated by this mechanism.

Language

English (en)

Chair and Committee

Sergej Djuranovic

Committee Members

Tim Schedl, James Skeath, Matthew Walter, Nicholas Davidson,

Comments

Permanent URL: https://doi.org/10.7936/K7Z037KK

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