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Series GSE198906 Query DataSets for GSE198906
Status Public on Dec 14, 2022
Title Control of pancreatic islet function and glucose homeostasis by a novel microexon program misregulated in type 2 diabetes
Organisms Homo sapiens; Mus musculus; Rattus norvegicus
Experiment type Expression profiling by high throughput sequencing
Summary Pancreatic islets control glucose homeostasis by the balanced secretion of insulin and other hormones, and its abnormal function causes diabetes or hypoglycemia. Here, we uncover a conserved program of alternative microexons included in mRNAs of islet cells, particularly in genes involved in vesicle transport and exocytosis. Islet microexons (IsletMICs) are regulated by the RNA binding protein SRRM3 and represent a subset of the larger neural program that are particularly sensitive to the levels of this protein. Both SRRM3 and IsletMICs are induced by elevated glucose levels, and depletion of SRRM3 in beta cell lines and mouse islets, or repression of particular IsletMICs using antisense oligonucleotides, leads to inappropriate insulin secretion. Consistently, SRRM3 mutant mice display defects in islet cell identity and function, leading to hyperinsulinemic hypoglycemia. Importantly, human genetic variants that influence SRRM3 expression and microexon inclusion in islets are associated with fasting glucose variation and type 2 diabetes risk.
 
Overall design Srrm3 was depleted or overexpressed in different systems to investigate regulation of microexons.
 
Contributor(s) Juan-Mateu J, Irimia M, Bonnal S, Bajew S
Citation(s) 36759540
Submission date Mar 17, 2022
Last update date Mar 15, 2023
Contact name Manuel Irimia
E-mail(s) [email protected]
Phone +34933160212
Organization name Centre for Genomic Regulation
Department Systems Biology Unit
Street address 88 Dr. Aiguader
City Barcelona
State/province Barcelona
ZIP/Postal code 08003
Country Spain
 
Platforms (3)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL18694 Illumina HiSeq 2500 (Rattus norvegicus)
Samples (25)
GSM5959884 HeLa cells overexpressing GFP
GSM5959885 HeLa cells with SRRM3 transgene, not dox induced
GSM5959886 HeLa cells with SRRM3 transgene, high dox induced
Relations
BioProject PRJNA817274

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Supplementary file Size Download File type/resource
GSE198906_RAW.tar 4.8 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file
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