DDX1 regulates alternative splicing and insulin secretion in pancreatic β cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA454378 | ENA |
REPOSITORIES: ENA
Similar Datasets
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
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
Project description:Alternative splicing (AS) is a fundamental mechanism for the regulation of gene expression. It affects more than 90% of human genes but its role in the regulation of pancreatic beta cells, the producers of insulin, remains unknown. Our recently published data indicated that the M-bM-^@M-^\neuron specificM-bM-^@M-^] Nova1 splicing factor is expressed in pancreatic beta cells. We have presently coupled specific knockdown (KD) of Nova1 with RNA-sequencing to determine all splice variants and downstream pathways regulated by this protein in beta cells. Nova1 KD altered the splicing of nearly 5000 transcripts. Pathway analysis indicated that these genes are involved in exocytosis, apoptosis, insulin receptor signalling, splicing and transcription. In line with these findings, Nova1 silencing inhibited insulin secretion and induced apoptosis basally and after cytokine treatment in rodent and human beta cells. These observations identify a novel layer of regulation of beta cell function, namely AS controlled by key splicing regulators such as Nova1. 3 batch of primary rat pancreatic beta cells were examined under 2 conditions: control and with Nova1 splicing factor knock-down
2014-10-01 | E-GEOD-59633 | biostudies-arrayexpress
Project description:A role for alternative splicing in circadian control of insulin secretion and glucose homeostasis
| PRJNA612358 | ENA
Project description:Type 2 Diabetes Mellitus (T2D), a multifactorial disease, can result from perturbations in numerous pancreatic genes. We describe a previously unanticipated role for Sox9, a transcriptional regulator of embryonic pancreas and endocrine cell development, in mature beta cells. Our data demonstrate that Sox9 has continued function in beta cells as they mature, and elimination of Sox9 compromises beta cell activities. Sox9-depleted rodent beta cells fail to appropriately secrete insulin and exhibit glucose intolerance in aging animals, mimicking the progressive degeneration observed in T2D. Human beta cells lacking SOX9 are functionally impaired with stunted first phase insulin secretion. In both rodent and human, Sox9 loss in beta cells disrupts alternative splicing patterns, with significant implications for maintenance of cellular function. Thus, our data uncover a novel, unprecedented role for a developmental transcription factor in mature beta cell function.
2023-10-18 | GSE245405 | GEO
Project description:Type 2 Diabetes Mellitus (T2D), a multifactorial disease, can result from perturbations in numerous pancreatic genes. We describe a previously unanticipated role for Sox9, a transcriptional regulator of embryonic pancreas and endocrine cell development, in mature beta cells. Our data demonstrate that Sox9 has continued function in beta cells as they mature, and elimination of Sox9 compromises beta cell activities. Sox9-depleted rodent beta cells fail to appropriately secrete insulin and exhibit glucose intolerance in aging animals, mimicking the progressive degeneration observed in T2D. Human beta cells lacking SOX9 are functionally impaired with stunted first phase insulin secretion. In both rodent and human, Sox9 loss in beta cells disrupts alternative splicing patterns, with significant implications for maintenance of cellular function. Thus, our data uncover a novel, unprecedented role for a developmental transcription factor in mature beta cell function.
2023-10-18 | GSE245404 | GEO
Project description:Alternative splicing (AS) is a fundamental mechanism for the regulation of gene expression. It affects more than 90% of human genes but its role in the regulation of pancreatic beta cells, the producers of insulin, remains unknown. Our recently published data indicated that the “neuron specific” Nova1 splicing factor is expressed in pancreatic beta cells. We have presently coupled specific knockdown (KD) of Nova1 with RNA-sequencing to determine all splice variants and downstream pathways regulated by this protein in beta cells. Nova1 KD altered the splicing of nearly 5000 transcripts. Pathway analysis indicated that these genes are involved in exocytosis, apoptosis, insulin receptor signalling, splicing and transcription. In line with these findings, Nova1 silencing inhibited insulin secretion and induced apoptosis basally and after cytokine treatment in rodent and human beta cells. These observations identify a novel layer of regulation of beta cell function, namely AS controlled by key splicing regulators such as Nova1.
2014-10-01 | GSE59633 | GEO
Project description:Lifestyle intervention including exercise restores glucose homeostasis and pancreatic β-cell function in type 2 diabetes (T2D). However, exercise compliance is a challenge. Novel alternative or adjuvant approaches are necessary. During exercise, the contracting skeletal muscle acts as endocrine organ via the secretion and endocrine signaling of functional proteins. We postulated that contracting skeletal muscle secretes proteins that target pancreatic β-cells and regulate insulin secretion and glucose metabolism. To test this hypothesis, we used an in vitro cell-based skeletal muscle contraction system to uncover proteins released in the muscle secretome. Using an RNAseq screen, we identified growth differentiation factor 15 (GDF15) as a lead candidate. β-cells, human pancreatic islets, and C57BL/6J mice exposed to acute GDF15 treatment exhibited increased glucose-stimulated insulin secretion, and the mechanism involved activation of the insulin release pathway. Chronic GDF15 treatment in db/db mice reduced insulin resistance and preserved pancreatic PDX-1 expression. Consistently, plasma GDF15 increased concurrently with C-peptide prior to the onset of chronic hyperglycemia in humans with pre-diabetes. In addition, in humans with T2D, exercise-induced GDF15 was associated with enhanced β-cell function. These findings support GDF15 as a potential therapeutic target for type 2 diabetes and associated co-morbidities.
2022-10-31 | GSE139872 | GEO
Project description:Progressive failure of insulin-producing beta cells is the central event leading to diabetes, yet the signalling networks controlling beta cell fate remain poorly understood. Here we show that SRp55, a splicing factor regulated by the diabetes susceptibility gene GLIS3, has a major role in maintaining function and survival of human beta cells. RNA-seq analysis revealed that SRp55 regulates the splicing of genes involved in cell survival and death, insulin secretion and JNK signalling. Specifically, SRp55-mediated splicing changes modulate the function of the pro-apoptotic proteins BIM and BAX, JNK signalling and endoplasmic reticulum stress, explaining why SRp55 depletion triggers beta cell apoptosis. Furthermore, SRp55 depletion inhibits beta cell mitochondrial function, explaining the observed decrease in insulin release. These data unveil a novel layer of regulation of human beta cell function and survival, namely alternative splicing modulated by key splicing regulators such as SRp55 that may crosstalk with candidate genes for diabetes.
2018-02-02 | GSE98485 | GEO
Project description:A distinct brain-β-cell circuit regulates insulin secretion
| PRJNA780516 | ENA