期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-020-19381-w
关键词
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资金
- Swiss National Science Foundation [310030-169480]
- Innovative Medicines Initiative 2 Joint Undertaking from European Union's Seventh Framework Programme (FP7/2007-2013) [115881, 115797]
- EFPIA
- JDRF
- Leona M. and Harry B. Helmsley Charitable Trust
- Swiss State Secretariat for Education, Research and Innovation (SERI) [16.0097]
- Placide Nicod foundation
- Swedish Research Council [2017-01090, 2019-01406]
- Diabetes Wellness Foundation Sweden
- Region Skane-ALF
- Swedish Diabetes Foundation
- Knut and Alice Wallenberg Foundation
- Swedish Foundation for Strategic Research (LUDC-IRC)
- strategic research area EXODIAB
- Horizon 2020 research and innovation programme
- Swedish Research Council [2019-01406, 2017-01090] Funding Source: Swedish Research Council
Fine-tuning of insulin release from pancreatic beta-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 beta-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 beta-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder.
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