PT  - JOURNAL ARTICLE
AU  - Jovana Vasiljević
AU  - Djordje Vasiljević
AU  - Katharina Ganß
AU  - Anke Sönmez
AU  - Carolin Wegbrod
AU  - Esteban Quezada
AU  - Carla Münster
AU  - Eyke Schöniger
AU  - Daniela Friedland
AU  - Nicole Kipke
AU  - Marius Distler
AU  - Matthias Selbach
AU  - Michele Solimena
TI  - Insulin mRNA is stored in RNA granules in resting beta cells
AID  - 10.1101/2021.05.07.443159
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.07.443159
4099  - http://biorxiv.org/content/early/2021/05/08/2021.05.07.443159.short
4100  - http://biorxiv.org/content/early/2021/05/08/2021.05.07.443159.full
AB  - The glucose-stimulated biosynthesis of insulin in pancreatic islet beta cells is post-transcriptionally regulated. Several RNA-binding proteins (RBPs) that regulate Insulin mRNA stability and translation also bind mRNAs coding for other insulin secretory granule (ISG) proteins. However, an overview of these interactions and their glucose-induced remodelling is still missing. Here we identify two distinct sets of RBPs which were preferentially pulled down with the 5’-UTRs of mouse Ins1, Ins2, spliced Ins2, Ica512/Ptprn and Pc2/Pcsk2 mRNAs from extracts of either resting or stimulated mouse insulinoma MIN6 cells compared to those recovered with the 5’-UTR of mouse Tubg1 encoding for γ-tubulin. Among RBPs binding in resting conditions to all tested transcripts for ISG components was hnRNP A2/B1. Hnrnpa2b1 KO MIN6 cells contained lower levels of Ins1 mRNA, proinsulin and insulin compared to control cells. In resting cells, both hnRNP A2/B1 and Insulin mRNAs localized to stress granules, which dissolved upon glucose stimulation. Insulin mRNA-positive RNA granules were also found in human pancreatic beta cells in situ. Our results suggest that resting beta cells store mRNAs for insulin secretory granule proteins in stress granules through specific RNA protein interactions. Glucose stimulation remodels these interactions, releasing the transcripts, and another set of RBPs coordinates their translation.Competing Interest StatementThe authors have declared no competing interest.