Project description:Our study shows that deletion of the alternative splicing regulator PQBP1 in striatal progenitors resulted in defective striatal development due to impaired neurogenesis of spiny projection neurons (SPNs). Therefore, we further reveal that PQBP1 associated with components in splicing machinery by LC-MS/MS. These findings identify PQBP1 as a novel regulator in balancing striatal progenitor proliferation and differentiation.
Project description:To investigate the comprehensive function of PQBP1 in the regulation of RNA splicing, we established Dox-inducible PQBP1 knockdown HEY cell line. We then performed gene expression profiling analysis using data obtained from RNA-seq of PQBP1 knockdown and control HEY cells (three biological replications of each sample).
Project description:Dysregulated expression of splicing factors has important roles in cancer development and progression. However, it remains a major challenge to identify the cancer-specific splicing variants. Here we demonstrated that splicing factor PQBP1 is commonly overexpressed in high-grade serous ovarian carcinoma (HGSOC) and high level of PQBP1 is associated with poor prognosis. To gain global insights into PQBP1-RNA binding property, RNA immunoprecipitation sequencing (RIP-seq) and SpyTag-based CLIP (SpyCLIP) were performed to analysis the interaction between PQBP1 and the target RNA.
Project description:Dysregulated expression of splicing factors has important roles in cancer development and progression. However, it remains a major challenge to identify the cancer-specific splicing variants. Here we demonstrated that splicing factor PQBP1 is commonly overexpressed in high-grade serous ovarian carcinoma (HGSOC) and high level of PQBP1 is associated with poor prognosis. To gain global insights into PQBP1-RNA binding property, RNA immunoprecipitation sequencing (RIP-seq) and SpyTag-based CLIP (SpyCLIP) were performed to analysis the interaction between PQBP1 and the target RNA.
Project description:To investigate the comprehensive function of PQBP1 in the regulation of RNA splicing, we established Dox-inducible PQBP1 knockdown HEY cell line. We then performed transcript expression profiling analysis using data obtained from long-read nanopore-seq of PQBP1 knockdown and control HEY cells (three biological replications of each sample).
Project description:DYRK1A is a protein kinase with several roles in brain development. This kinase is involved in two intellectual disability syndromes: Down syndrome and DYRK1A haploinsufficiency syndrome. The Dyrk1a+/- mouse is a model for DYRK1A haploinsufficiency syndrome. We used microarray to evaluate the impact of DYRK1A haploinsufficiency in the development of the cerebral cortex.
Project description:The balance between cell proliferation and differentiation is essential for maintaining the neural progenitor pool and brain development. Although the mechanisms underlying cell proliferation and differentiation at the transcriptional level have been studied intensively, post-transcriptional regulation of cell proliferation and differentiation remains largely unclear. Here, we show that deletion of the alternative splicing regulator PQBP1 in striatal progenitors resulted in defective striatal development due to impaired neurogenesis of spiny projection neurons (SPNs). Pqbp1 deficiency striatal progenitors exhibit declined proliferation and increased differentiation, resulting in a reduced striatal progenitor pool. We further reveal that PQBP1 associates with components in splicing machinery. The alternative splicing profiles identify that PQBP1 promotes the exon 9 inclusion of Numb, a variant that mediates progenitor proliferation. These findings identify PQBP1 as a novel regulator in balancing striatal progenitor proliferation and differentiation and provide alternative insights into the pathogenic mechanisms underlying Renpenning syndrome.
