The Enzymes Responsible for the Addition and Maintenance of the 3' Oligouridylation of histone mRNA

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Lackey, Patrick
- Affiliation: School of Medicine, Department of Biochemistry and Biophysics

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Histone mRNAs end in a highly conserved 3’ stemloop, making them the only known metazoan mRNAs that do not end in a poly(A) tail. They are also tightly cell-cyle regulated, with expression increasing 30-fold at the beginning of S-phase followed by a quick reduction in half-life as S-phase ends. Because of its unique 3’ ends, histone mRNAs require a different mechanism to initiate degradation than bulk mRNA. Previous work has revealed that initiation of histone mRNA degradation is mediated by an oligouridylation at the 3’ end of the message. Further work showed these oligouridylations vary widely in base position, length, and when they are added to the message. In this thesis, I use a high-throughput sequencing approach to show that the oligouridylation of the 3’ UTR of histone mRNA are added by the enzyme TUT7 and that the length and function of the oligouridylations is controlled by the human 3’ exonuclease, 3’hExo; during S-phase the U tails are 1-2 nts and function to protect the 3’ end of the message from degradation. As S-phase ends, longer U-tails are added and 3’hExo initiates the degradation of the message. From the next-generation sequencing data, I also present evidence that oligouridylation of the open reading frame is added differently than the oligouridylation of the 3’ end, likely by a different enzyme.

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