The Functional Characterization of the N-terminal Domains of TUT4
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.