Either DIS3 substrates or the RNA exosome-mediated transcription termination that are dysregulated by DIS3 knockout can directly affect local chromatin structure.36 Dysregulated genes (MTAP, G3BP2, SEC23IP, USO1) in homozygous Dis3 null embryos mirror those found in the most common form of melanoma (GEO: GSE22301),37 which also has decreased levels of Dis3. Here, SEC23IP is linked to melanoma.