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Status |
Public on Sep 21, 2020 |
Title |
A circular RNA generated from an intron of the insulin gene controls insulin secretion |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of β-cells, resulting in impaired glucose- or KCl-induced insulin release and calcium signaling. The effect of the circular RNA is exerted at the transcriptional level and involves an interaction with the RNA-binding protein TAR DNA-binding protein 43 kDa (TDP-43). The level of this circularized intron is reduced in the islets of rodent diabetes models and of type 2 diabetic patients, possibly explaining their impaired secretory capacity. The study of this and other circular RNAs helps understanding β-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder.
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Overall design |
Mouse islet circRNA annotation and RNA-seq of rat islet cells transfected with control or ci-Ins2 gapmeRs (n = 3 samples per treatment).
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Contributor(s) |
Stoll L, Rodríguez-Trejo A, Guay C, Brozzi F, Bayazit MB, Gattesco S, Menoud V, Sobel J, Marques AC, Venø MT, Esguerra JS, Barghouth M, Suleiman M, Marselli L, Kjems J, Eliasson L, Renström E, Bouzakri K, Pinget M, Marchetti P, Regazzi R |
Citation(s) |
33154349 |
Submission date |
Jul 23, 2019 |
Last update date |
Nov 12, 2020 |
Contact name |
Adriana Rodriguez Trejo |
Organization name |
UNIL
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Department |
DNF
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Lab |
Pr. Romano Regazzi
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Street address |
Rue du Bugnon 9
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City |
Lausanne |
State/province |
Vaud |
ZIP/Postal code |
1005 |
Country |
Switzerland |
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Platforms (1) |
GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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Samples (6)
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Relations |
BioProject |
PRJNA556164 |
SRA |
SRP216015 |
Supplementary file |
Size |
Download |
File type/resource |
GSE134699_Gene_expression_ci-Ins2_knockdown.xlsx |
2.9 Mb |
(ftp)(http) |
XLSX |
GSE134699_Mouse_islet_circRNA_annotation.xlsx |
3.7 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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