Tut4, also known as Zcchc11, TENT3A, or Z11, is a terminal uridylyltransferase. It plays a crucial role in regulating miRNA and mRNA homeostasis through 3' end uridylation [2,3,4,5,6]. This process is involved in various biological pathways such as controlling the stability of transcripts, and is important for maintaining the normal state of the transcriptome and cell functions. Genetic models like gene knockout (KO) are valuable for studying Tut4's functions.

In the context of coronavirus infection, depletion of host Tut4/7 leads to increased replication capacity of the mouse hepatitis virus (MHV), indicating that Tut4/7-mediated uridylation of MHV subgenomic RNAs marks them for decay and delays viral replication [1]. In miRNA and mRNA regulation, disruption of Tut4/7 expression in cells increases the abundance of various miRNAs, especially the let-7 family, and affects the levels of many of their mRNA targets. The mRNAs coding for proteins involved in cellular stress response, rRNA processing, etc., are most affected in Tut4/7 knockout cells [2]. Also, in cancer cell lines, mutation of Tut4/7 significantly reduces miRNA uridylation, causing defects in cancer cell properties like proliferation and migration, and leading to deregulation of miRNA-mRNA networks in a cell-type-specific manner [4].

In summary, Tut4 is essential for regulating RNA stability and abundance through uridylation, impacting multiple biological processes. Studies using KO models have revealed its roles in viral replication, miRNA/mRNA homeostasis, and cancer-related cell functions, providing insights into potential therapeutic strategies for viral diseases and cancer.