Project description:Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer with high lethality rate. In this study, we identify that terminal Uridylyl Transferase 1 (TUT1), a specific terminal uridylyltransferase for U6 snRNA, is required for survival of PDAC, but not for that of normal adult pancreas. Mechanistically, TUT1 uridylylation activity promotes tri-snRNP assembly though facilitating the binding of LSM protein to U6 snRNA. TUT1 deletion leads to global alternative splicing (AS) changes which in turn triggers PDAC cell cycle dysregulation. Here, we reveal a novel function of TUT1 in regulating AS by modulating tri-snRNP levels and identify TUT1 as a potential therapeutic target for the treatment of PDAC.
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer with high lethality rate. In this study, we identify that terminal Uridylyl Transferase 1 (TUT1), a specific terminal uridylyltransferase for U6 snRNA, is required for survival of PDAC, but not for that of normal adult pancreas. Mechanistically, TUT1 uridylylation activity promotes tri-snRNP assembly though facilitating the binding of LSM protein to U6 snRNA. TUT1 deletion leads to global alternative splicing (AS) changes which in turn triggers PDAC cell cycle dysregulation. Here, we reveal a novel function of TUT1 in regulating AS by modulating tri-snRNP levels and identify TUT1 as a potential therapeutic target for the treatment of PDAC.
Project description:Alternative splicing is a key event to human transcriptome and proteome diversity and complexity. Recent evidence suggests that pancreatic cancer might possess particular patterns of splice variation that influence the function of individual genes contributing to tumour progression in this disease. The identification of new pancreatic cancer-associated splice variants would offer opportunities for novel diagnostics and potentially also represent novel therapeutic targets. In this dataset, we investigated the alterations in the splicing machinery in pancreatic adenocarcinoma (PDAC) specimens with full clinicopathological details, in comparisons to adjacent pancreatic tissues and normal tissues from donors.
Project description:Alternative splicing is a key event to human transcriptome and proteome diversity and complexity. Recent evidence suggests that pancreatic cancer might possess particular patterns of splice variation that influence the function of individual genes contributing to tumour progression in this disease. The identification of new pancreatic cancer-associated splice variants would offer opportunities for novel diagnostics and potentially also represent novel therapeutic targets. In this dataset, we investigated the alterations in the splicing machinery in pancreatic adenocarcinoma (PDAC) specimens with full clinicopathological details, in comparisons to adjacent pancreatic tissues and normal tissues from donors.
Project description:This SuperSeries is composed of the following subset Series: GSE31485: CTCF promotes RNA pol II pausing and links DNA methylation to alternative splicing [ChIP-Seq] GSE31486: CTCF promotes RNA pol II pausing and links DNA methylation to alternative splicing [RNA-Seq] Refer to individual Series