ArticleNature metabolism2023
Pancreatic microexons regulate islet function and glucose homeostasis.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 26 citations in OpenAlex.
- Neuronal microexons modulate arousal via the cAMP-PKA-CREB pathway in zebrafish.Science advances · 2026Article
- Efficient co-transcriptional splicing enforces rapid microexon definition and inclusion by SRRM4.bioRxiv : the preprint server for biology · 2026Article
- Phenotypic impact of individual conserved neuronal microexons and their master regulators in zebrafish.eLife · 2025Article
- Global DNA methylation signatures associated with chemoresistance and poor prognosis of high grade serous ovarian cancer.Scientific reports · 2025Article
- Core splicing architecture and early spliceosomal recognition determine microexon sensitivity to SRRM3/4.Nature structural & molecular biology · 2025Article
- Identification of immunosuppressive CD4Discover oncology · 2025Article
- HNF1A and A1CF coordinate a beta cell transcription-splicing axis that is disrupted in type 2 diabetes.Cell metabolism · 2025Article
- Deep indel mutagenesis reveals the regulatory and modulatory architecture of alternative exon splicing.Nature communications · 2025Article
- Orchestrating Nutrient Homeostasis: RNA-Binding Proteins as Molecular Conductors in Metabolic Disease Pathogenesis.Nutrients · 2025Review
- Unveiling a Microexon Switch: Novel Regulation of the Activities of Sugar Assimilation and Plant-Cell-Wall-Degrading Xylanases and Cellulases by Xlr2 inInternational journal of molecular sciences · 2024Article
- Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma.World journal of diabetes · 2024Article
- FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer.Cell death discovery · 2024Review
- Unique transcriptomes of sensory and non-sensory neurons: insights from Splicing Regulatory States.Molecular systems biology · 2024Review
- Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents.International journal of molecular sciences · 2023Review
- Small but mighty: microexons in glucose homeostasis.Trends in genetics : TIG · 2023Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic islets control glucose homeostasis by the balanced secretion of insulin and other hormones, and their abnormal function causes diabetes or hypoglycaemia. Here we uncover a conserved programme 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 programme that are particularly sensitive to SRRM3 levels. Both SRRM3 and IsletMICs are induced by elevated glucose levels, and depletion of SRRM3 in human and rat beta cell lines and mouse islets, or repression of particular IsletMICs using antisense oligonucleotides, leads to inappropriate insulin secretion. Consistently, mice harbouring mutations in Srrm3 display defects in islet cell identity and function, leading to hyperinsulinaemic hypoglycaemia. Importantly, human genetic variants that influence SRRM3 expression and IsletMIC inclusion in islets are associated with fasting glucose variation and type 2 diabetes risk. Taken together, our data identify a conserved microexon programme that regulates glucose homeostasis.
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