Project description:The RNA-binding protein Snd1 can regulate gene expression through various mechanisms, including microRNA decay. Here we have investigated microRNA expression in livers of WT and Snd1 knockout (KO) mice
Project description:PyMT tumor cells with indicated status of Mtdh and Snd1 were treated with camptothecin (CPT) and the transcirptome profiles were determined and compared two sets of experiments: (1) vector control vs Snd1-KD under CPT treament (2) PyMT/Mtdh-KO cells reconstituted with either WT or Snd1-binding deficient mutant Mtdh (W391D) under CPT treatment
Project description: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.
Project description:To investigate the roles of Klf3 in B lymphopoiesis, CD19+ B cells were sorted from the spleens of WT and Klf3 KO mice (Molecular and Cellular Biology (2008); 28:3967–3978). Following RNA extraction, gene expression was compared in WT and Klf3 KO CD19+splenic B cells using Affymetrix microarrays.
Project description:Staphylococcal nuclease and Tudor domain containing 1 (SND1) is a multifunctional protein with four SN domains and a Tudor domain that recognizes symmetric dimethylarginine (SDMA) modifications. Although highly enriched in the pancreas, its role in this tissue remains unclear. Here, we show that loss of SND1 SDMA-reader activity—via knockout or a Y766L point mutation in the Tudor domain—leads to reduced S6 phosphorylation. Mechanistically, SND1 binds SDMA-modified arginines within the C-terminal glycine- and arginine-rich (GAR) motif of S6K2, a kinase also highly expressed in the pancreas. To evaluate the functional relevance of this interaction, we generated S6k2 RK mice carrying lysine substitutions at the GAR arginines, which abolished SND1 recognition. Transcriptomic profiling revealed a strong overlap in dysregulated genes and pathways—including the unfolded protein response and metabolic programs between Snd1 KI and S6k2 RK pancreata. These findings define a methylation-dependent SND1-S6K2 signaling axis as a critical regulator of pancreatic homeostasis.
Project description:To investigate the roles of Klf3 in B lymphopoiesis, CD19+ B cells were sorted from the spleens of WT and Klf3 KO mice (Molecular and Cellular Biology (2008); 28:3967–3978). Following RNA extraction, gene expression was compared in WT and Klf3 KO CD19+splenic B cells using Affymetrix microarrays. 4 wildtype and 4 Klf3 KO mice were analysed, aged between 10 and 12 weeks
