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| Status |
Public on Feb 02, 2018 |
| Title |
A SRp55-regulated alternative splicing network controls pancreatic beta cell survival and function |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
Five independent preparations of EndoC-βH1 cells exposed to control (siCTL) or SRp55 (siSR#2) siRNAs
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| Contributor(s) |
Mateu JJ, Alvelos MI, Turatsinze J, Eizirik DL |
| Citation(s) |
29246973, 33376132 |
| |
| Submission date |
May 02, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Jonas Juan Mateu |
| E-mail(s) |
mjuanmat@ulb.ac.be
|
| Phone |
003225556107
|
| Organization name |
Universite Libre de Bruxelles
|
| Department |
Faculty of Medecine
|
| Lab |
ULB Center for Diabetes Research
|
| Street address |
Route de Lennik 808 CP 618
|
| City |
Brussels |
| ZIP/Postal code |
1070 |
| Country |
Belgium |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (10)
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| Relations |
| BioProject |
PRJNA385196 |
| SRA |
SRP106195 |
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