DIS3-like 3'-5' exoribonuclease 2 (DIS3L2)

DIS3-like 3'-5' exoribonuclease 2 (DIS3L2) is a highly conserved cytoplasmic exoribonuclease in the RNase II/R family, specialized for 3'-5' hydrolytic degradation of uridylated RNA substrates, including miRNAs, pre-miRNAs, mRNAs, and non-coding RNAs[2][4]. DIS3L2 is critical for RNA quality control, developmental proliferation, and differentiation[1][2][4]. Loss-of-function mutations cause the overgrowth disorder Perlman syndrome and are strongly implicated in pediatric Wilms’ tumor pathogenesis[1][2][4]. DIS3L2’s biological importance spans cell division, cell cycle regulation, and apoptosis, where its absence can deregulate key signaling pathways such as PI3-Kinase/AKT, resulting in tissue hyperplasia or tumorigenesis[1][2][4]. No approved drugs directly target DIS3L2, but pathway modulation (e.g., PI3K inhibitors) can counteract proliferation effects in DIS3L2-deficient models[1]. Its high processivity and capability to degrade structured RNA without cofactors distinguish DIS3L2 from most other RNA exosome nucleases[4].

Other names

FAM6AhDIS3L2FLJ36974MGC42174PRLMNSDIS3 mitotic control homolog-like 2Family with sequence similarity 6, member A

Hydrolytic 3’-5’ exonucleolytic degradation of uridylated RNA substrates (including miRNA, pre-miRNA, ncRNAs, and aberrant mRNAs) Negative control of growth-promoting and cell cycle-regulating RNA species (mutational loss results in upregulation of growth signals such as Idgf2/IGF2 and hyperactivation of PI3-Kinase/AKT signaling) RNA quality control, particularly preventing the translation of defective or aberrant transcripts