Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nova1 is a master regulator of alternative splicing in pancreatic beta cells

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE59633 | GEO | 2014/10/01

SECONDARY ACCESSION(S): PRJNA255786

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Nova1 is a master regulator of alternative splicing in pancreatic beta cells

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

RNAseq in E18.5 wild-type, Nova2-KO, and Nova1-KO mouse cortex and mid- and hind-brain

Project description:We sequenced mRNA from E18.5 mouse cortex (3 wild-type vs 3 Nova2-/- and 3 wild-type vs 3 Nova1-/-) and from E18.5 mouse mid- and hind-brain (3 wild-type vs 3 Nova1-/-) to compare gene expression level and alternative splicing events between wild-type and Nova mutant mice.

2016-05-26 | GSE69709 | GEO

Effects of Nova1 Deletion on Gene Expression in Tissues and Cells

Project description:To elucidate the function of Nova1 in neurons, especially in inhibitory neurons, gene expression profiling analysis (RNAseq, TRAP-seq) was performed using Nova1 conditional knockout mice and their primary neurons.

2024-08-15 | GSE212473 | GEO

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

Loss of tetraspanin-7 expression reduces pancreatic beta-cell exocytosis Ca2+ sensitivity but has limited effect on systemic metabolism [human]

Project description:Background: Tetraspanin-7 (Tspan7) is an islet autoantigen involved in autoimmune type 1 diabetes and known to regulate beta-cell L-type Ca2+ channel activity. However, the role of Tspan7 in pancreatic beta-cell function is not yet fully understood. Methods: Histological analyses were conducted using immunostaining. Whole-body metabolism was tested using glucose tolerance test. Islet hormone secretion was quantified using static batch incubation or dynamic perifusion. Beta-cell transmembrane currents, electrical activity and exocytosis were measured using whole-cell patch-clamping and capacitance measurements. Gene expression was studied using mRNA-sequencing and quantitative PCR. Results: Tspan7 is expressed in insulin-containing granules of pancreatic beta-cells. Tspan7-knockout mice (Tspan7 y/- mouse) exhibit reduced body weight and ad libitum plasma glucose but normal glucose tolerance. Tspan7y/- islets have normal insulin content and glucose- or tolbutamide-stimulated insulin secretion. Depolarisation-triggered Ca2+ current was enhanced in Tspan7y/- beta-cells, but beta-cell electrical activity and depolarisation-evoked exocytosis were unchanged suggesting that exocytosis was less sensitive to Ca2+. TSPAN7 knockdown (KD) in human pseudo-islets led to a significant reduction in high K+-stimulated insulin secretion. Transcriptomic analyses show that TSPAN7 KD in human pseudo-islets correlated with changes in genes involved in hormone secretion, apoptosis and ER stress. Consistent with rodent beta-cells, exocytotic Ca2+ sensitivity was reduced in a human beta cell line (EndoC-H1) following Tspan7 KD. Conclusion: Tspan7 is involved in the regulation of Ca2+-dependent exocytosis in beta-cells. Its function is more significant in human beta-cells than their rodent counterparts

2022-10-10 | GSE213730 | GEO

Loss of tetraspanin-7 expression reduces pancreatic beta-cell exocytosis Ca2+ sensitivity but has limited effect on systemic metabolism [mouse]

Project description:Background: Tetraspanin-7 (Tspan7) is an islet autoantigen involved in autoimmune type 1 diabetes and known to regulate beta-cell L-type Ca2+ channel activity. However, the role of Tspan7 in pancreatic beta-cell function is not yet fully understood. Methods: Histological analyses were conducted using immunostaining. Whole-body metabolism was tested using glucose tolerance test. Islet hormone secretion was quantified using static batch incubation or dynamic perifusion. Beta-cell transmembrane currents, electrical activity and exocytosis were measured using whole-cell patch-clamping and capacitance measurements. Gene expression was studied using mRNA-sequencing and quantitative PCR. Results: Tspan7 is expressed in insulin-containing granules of pancreatic beta-cells. Tspan7-knockout mice (Tspan7 y/- mouse) exhibit reduced body weight and ad libitum plasma glucose but normal glucose tolerance. Tspan7y/- islets have normal insulin content and glucose- or tolbutamide-stimulated insulin secretion. Depolarisation-triggered Ca2+ current was enhanced in Tspan7y/- beta-cells, but beta-cell electrical activity and depolarisation-evoked exocytosis were unchanged suggesting that exocytosis was less sensitive to Ca2+. TSPAN7 knockdown (KD) in human pseudo-islets led to a significant reduction in high K+-stimulated insulin secretion. Transcriptomic analyses show that TSPAN7 KD in human pseudo-islets correlated with changes in genes involved in hormone secretion, apoptosis and ER stress. Consistent with rodent beta-cells, exocytotic Ca2+ sensitivity was reduced in a human beta cell line (EndoC-bH1) following Tspan7 KD. Conclusion: Tspan7 is involved in the regulation of Ca2+-dependent exocytosis in beta-cells. Its function is more significant in human beta-cells than their rodent counterparts

2022-10-10 | GSE213729 | GEO

NOVA1 HITS-CLIP in wild-type mouse diencephalon/ mesencephalon (P21)

Project description:Mouse diencephalon/ mesencephalon samples from P21 wild-type were subjected to HITS-CLIP to detect NOVA1 binding positions on RNA

2024-08-15 | GSE212547 | GEO

Rattus norvegicus

Project description:Nova1 is a master regulator of alternative splicing in pancreatic beta cells

| PRJNA255786 | ENA

NOVA2 and NOVA1 HITS-CLIP in wild-type mouse cortex (E18.5)

Project description:Mouse cortex samples from E18.5 wild-type were subjected to HITS-CLIP to detect NOVA2 and NOVA1 binding positions on RNA

2016-05-26 | GSE69710 | GEO

SMNDC1 links chromatin remodeling and splicing to regulate pancreatic hormone expression

Project description:Insulin expression is restricted to the pancreatic beta cells, which are physically or functionally depleted in diabetes. Identifying targetable pathways repressing insulin in non-beta cells, particularly in the developmentally related glucagon-secreting alpha cells, is an important aim of regenerative medicine. Here, we performed an RNA interference screen in the murine alpha cell line, alphaTC1, to identify silencers of insulin expression. We discovered that knockdown of the splicing factor Smndc1 (Survival Motor Neuron Domain Containing 1) triggered a global repression of alpha cell gene-expression programs in favor of increased beta cell markers. Mechanistically, Smndc1 knockdown upregulated the key beta cell transcription factor Pdx1, by modulating the activities of the BAF and Atrx families of chromatin remodeling complexes. SMNDC1’s repressive role was conserved in human pancreatic islets, its loss triggering enhanced insulin secretion and PDX1 expression. Our study identifies Smndc1 as a key factor connecting splicing and chromatin remodeling to the control of insulin expression in human and mouse islet cells.

2022-07-01 | PXD030363 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data