Terminal uridyltransferase 4 (TUT4) (TUT4)

Terminal uridyltransferase 4 (TUT4), also known as ZCCHC11, is a nucleotidyltransferase that catalyzes the addition of uridine residues to the 3' end of various RNA molecules, a process known as uridylation [UniProt: Q5TAX3]. Its most prominent role is in the LIN28-mediated pathway, where it polyuridylates pre-let-7 microRNA, thereby blocking its maturation and marking it for degradation by the exonuclease DIS3L2 [PubMed: 19703396]. Since let-7 is a critical tumor suppressor that regulates oncogenes like MYC and RAS, the overexpression of TUT4 is frequently associated with cancer progression and poor prognosis in various malignancies [PubMed: 22544147]. Beyond miRNA regulation, TUT4 is involved in the uridylation of histone mRNAs and the regulation of cytokine mRNA stability, such as IL-6, which links it to inflammatory processes [PubMed: 21078962]. In the context of infectious diseases, TUT4 has been shown to influence the replication of certain viruses by modifying viral RNA [PubMed: 25691595]. Consequently, TUT4 is being actively investigated as a therapeutic target, with research focusing on small-molecule inhibitors that can restore let-7 levels and inhibit tumor growth [PubMed: 30104379].

Other names

ZCCHC11Zinc finger CCHC domain-containing protein 11PAP-associated domain-containing protein 3PAPD3RNA-binding region-containing protein 3

Inhibition of terminal uridylation of RNA substrates, particularly pre-let-7 miRNA, to prevent their degradation and restore normal gene expression patterns.