Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biochemistry

Supervisor

Heinemann, Ilka U.

Abstract

Cells have the ability to adapt in response to environmental stressors by regulating RNA stability. Terminal uridylyltransferases (TUTases) have emerged as essential enzymes in post-transcriptional regulation. TUTases catalyze the untemplated addition of uridine residues to the RNA 3’-end, which generally leads to RNA degradation. Human TUTase 4 (TUT4) regulates mRNA and miRNA stability by initiating the decay of RNA through the addition of a poly(U) tail. TUT4 encodes two catalytic regions. Previously, the C-terminal catalytic motif was thought to execute uridylation activity, while the N-terminal motif was thought to be catalytically inactive. I here demonstrate that while less active than its Cterminal counterpart, the N-terminal motif is indeed capable of post-transcriptional RNA editing and displays RNA substrate specificity. I further identified one of the three catalytic aspartates required for uridylation activity. This reveals a previously unknown catalytic function of the N-terminal catalytic domains with implications for its biological function.

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