Terminal uridylyltransferase 4 (TUT4)

Terminal uridylyltransferase 4 (TUT4, also known as ZCCHC11) is a noncanonical RNA nucleotidyltransferase enzyme primarily responsible for catalyzing the addition of uridine residues to the 3′ ends of specific RNA transcripts in a template-independent manner[1][2][3][4]. TUT4 regulates microRNA biogenesis—most notably by uridylating pre-let-7 miRNA in a process modulated by the RNA-binding protein Lin28, either promoting or suppressing let-7 maturation depending on the context. In addition, TUT4 collaborates with TUT7 to mark mRNAs with short poly(A) tails for decay, playing a key role in post-transcriptional surveillance. TUT4 is essential for replication-dependent histone mRNA turnover after DNA replication arrest and can modulate immune responses through its effects on cytokine-targeting miRNAs. The enzyme contains zinc finger domains and has a duplicated nucleotidyltransferase catalytic domain, with one active site. Its broad RNA substrate spectrum and post-transcriptional gene regulatory effects implicate TUT4 in cancer, stem cell biology, inflammation, and other processes[1][2][3][4].

Other names

ZCCHC11KIAA0191PAPD3TENT3AZinc finger CCHC domain-containing protein 11TUTase 4

Any future drugs/inhibitors would likely act through inhibiting the catalytic uridylyl transfer activity, thus impacting miRNA processing, mRNA stability, or histone mRNA turnover. Modulating TUT4 may alter let-7 microRNA maturation, miRNA/mRNA degradation rates, and cytokine levels.