Back

Control of pancreatic islet function and glucose homeostasis by a novel microexon program misregulated in type 2 diabetes

Juan-Mateu, J.; Bajew, S.; Miret-Cuesta, M.; Iniguez, L. P.; Lopez-Pascual, A.; Bonnal, S.; Atla, G.; Bonas-Guarch, S.; Ferrer, J.; Valcarcel, J.; Irimia, M.

2022-10-22 molecular biology
10.1101/2022.04.02.486809 bioRxiv
Show abstract

Pancreatic islets control glucose homeostasis by the balanced secretion of insulin and other hormones, and their 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 regulator. 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 IsletMIC inclusion in islets are associated with fasting glucose variation and type 2 diabetes risk.

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

1
Nature Communications
○ 5641 papers in training set
Top 6%
22.5%
Similar papers in this journal
2
Nature
○ 645 papers in training set
Top 0.6%
18.6%
Similar papers in this journal
3
Nature Structural & Molecular Biology
236 papers in training set
Top 0.2%
15.0%
50% of probability mass above
4
Nature Metabolism
○ 69 papers in training set
Top 0.3%
5.5%
Similar papers in this journal
5
Nature Genetics
○ 286 papers in training set
Top 2%
3.5%
Similar papers in this journal
6
Nature Cell Biology
○ 118 papers in training set
Top 0.9%
3.2%
7
Cell Reports
○ 1498 papers in training set
Top 15%
2.4%
8
Cell
○ 431 papers in training set
Top 5%
2.1%
9
Molecular Cell
○ 350 papers in training set
Top 3%
2.1%
10
eLife
● 5828 papers in training set
Top 48%
1.9%
11
Science
● 477 papers in training set
Top 5%
1.7%
12
Science Advances
● 1243 papers in training set
Top 20%
1.7%
13
Cell Genomics
○ 172 papers in training set
Top 3%
1.5%
14
Genes & Development
● 90 papers in training set
Top 1%
1.3%
15
Nature Chemical Biology
○ 119 papers in training set
Top 2%
1.1%
16
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 34%
1.1%
17
Cell Discovery
○ 57 papers in training set
Top 0.7%
1.1%
18
Cell Metabolism
○ 57 papers in training set
Top 1.0%
1.1%
19
Nature Methods
○ 385 papers in training set
Top 6%
1.1%
20
Cell Stem Cell
○ 62 papers in training set
Top 1%
1.0%
21
Nucleic Acids Research
◐ 1281 papers in training set
Top 13%
0.9%
22
Nature Biotechnology
○ 172 papers in training set
Top 5%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.