TUT4 (terminal uridylyl transferase 4) is a uridylyltransferase that catalyzes 3' uridylation of RNAs, playing critical roles in post-transcriptional gene regulation. Primary function: TUT4 mediates terminal uridylation of mRNAs with short poly(A) tails, facilitating global mRNA decay 1. It also regulates miRNA biogenesis through multiple uridylation mechanisms, acting as a suppressor by mediating terminal uridylation of pre-miRNAs including let-7, miR-107, miR-143, and miR-200c, triggering their degradation 2. TUT4 uridylates most mature miRNAs and functions redundantly with TUT7 3. Mechanism: TUT4 operates through both mono- and oligo-uridylation pathways. Monouridylation of pre-let-7 in the absence of LIN28A promotes optimal 3' end formation for Dicer processing 2, while oligo-uridylation (mediated by LIN28A) blocks Dicer processing and promotes degradation by DIS3L2 4. TUT4 cooperates with TUT7 and MOV10 to suppress LINE-1 retrotransposition by destabilizing mRNAs in cytoplasmic ribonucleoprotein granules. Disease relevance: TUT4/7 dysfunction correlates with early embryonic developmental arrest in human preimplantation embryos 5, and TUT4/7 inhibition shows therapeutic potential in FOCAD-deficient cancers 6. Clinical significance: TUT4 represents a viable pharmacological target, with selective TUT4/7 inhibitors demonstrating antiproliferative activity in specific cancer contexts 6.