The methylarginine reader function of SND1 is oncogenic

Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that “reads” methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. SND1 is a known driver of hepatocellular carcinoma, but it is unknown if the Tudor domain is needed to drive this disease. We sought to identify the biological role of the SND1 Tudor domain in normal and tumorigenic settings. To do so, we developed two genetically engineered SND1 mouse models, namely a knockout (Snd1 KO) and a Snd1 Tudor domain mutated (Snd1 KI) mouse. Transcriptome analysis of normal KO and KI liver samples reveals a role for the SND1 Tudor domain in regulating expression of major acute phase proteins (APPs) and genes involved in the unfolded protein response (UPR), which could provide mechanistic insight into SND1's functions in a tumor setting. These processes may provide insight into how SND1 functions as an oncogene. These results support the use of PRMT5 inhibitors, and the development of small molecule inhibitors that target the SND1 Tudor domain, as novel treatments for HCC. Overall design: To understand the transcriptional consequences of SND1 Tudor domain, we harvested total RNA from livers of SND1 WT, SND1 KO, and SND1 Tudor domain mutant (SND1 KI) mice to perform RNA-seq.