Project description:Recent studies have identified dysregulation of RNA-binding proteins (RBPs) and aberrant mRNA splicing in the onset of diseases including diabetes. Here we investigated the role of RBFOX2 in the pancreatic β cell through the conditional mutation of Rbfox2 in the mouse pancreas (Pdx1:Cre; Rbfox2fl/lf) and RNAi experiments in the mouse insulinoma cell line, MIN6. We then identified the direct targets of RBFOX2 in the mouse β cell transcriptome my eCLIP-Seq in MIN6 cells.

2023-09-25 | GSE221274 | GEO

Modulation of insulin secretion through RBFOX2-mediated alternative splicing [eCLIP-Seq MIN6]

2023-09-25 | GSE221276 | GEO

Modulation of insulin secretion through RBFOX2-mediated alternative splicing [RNA-seq Mouse Iselt]

2023-09-25 | GSE221275 | GEO

Modulation of insulin secretion by RBFOX2-mediated alternative splicing.

Project description:Insulin secretion is a tightly regulated process that is vital for maintaining blood glucose homeostasis. Although the molecular components of insulin granule trafficking and secretion are well established, how they are regulated to rapidly fine-tune secretion in response to changing environmental conditions is not well characterized. Recent studies have determined that dysregulation of RNA-binding proteins (RBPs) and aberrant mRNA splicing occurs at the onset of diabetes. We demonstrate that the RBP, RBFOX2, is a critical regulator of insulin secretion through the alternative splicing of genes required for insulin granule docking and exocytosis. Conditional mutation of Rbfox2 in the mouse pancreas results in decreased insulin secretion and impaired blood glucose homeostasis. Consistent with defects in secretion, we observe reduced insulin granule docking and corresponding splicing defects in the SNARE complex components. These findings identify an additional mechanism for modulating insulin secretion in both healthy and dysfunctional pancreatic β cells.

| S-EPMC10676425 | biostudies-literature

DDX1 regulates alternative splicing and insulin secretion in pancreatic β cells

Project description:DEAD-box helicase 1 (DDX1) is a multifunction protein involved in diverse cellular processes including transcription, viral replication, mRNA/miRNA processing, and tRNA splicing. Here, we report a novel function of DDX1 in mRNA alternative splicing in pancreatic β cells. By performing integrated data analysis of high-throughput RNA sequencing (RNA-Seq), and cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq), we identify hundreds of alternative splicing genes that are targeted by DDX1. These DDX1-targeted alternative splicing genes are mainly associated with calcium ion binding, high voltage-gated calcium channel, and transmembrane transporter. Functionally, silencing DDX1 impairs calcium influx and insulin secretion in the pancreatic β cells. These results reveal an important role for DDX1 in the regulation of gene alternative splicing and insulin secretion in pancreatic β cells.

2018-05-02 | GSE113893 | GEO

Modulation of insulin secretion through RBFOX2-mediated alternative splicing

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-25 | GSE221277 | GEO

A role for alternative splicing in circadian control of insulin secretion and glucose homeostasis

Project description:We report the discovery of circadian clock-controlled alterantive pre-mRNA splicing in pancreatic beta cells and its role in insulin secretion. We performed RNA-sequencing in CRISPR-CAS9 edited Clock and Bmal1 knockout BetaTC6 cells and used differential mRNA expression and splicing analysis to identify and validate transcriptional and alternative splicing targets of the circadian clock regulating insulin secretion.

2020-08-10 | GSE146916 | GEO

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