Frontiers in Endocrinology (Aug 2022)

Glucose controls co-translation of structurally related mRNAs via the mTOR and eIF2 pathways in human pancreatic beta cells

  • Manuel Bulfoni,
  • Costas Bouyioukos,
  • Albatoul Zakaria,
  • Fabienne Nigon,
  • Roberta Rapone,
  • Laurence Del Maestro,
  • Slimane Ait-Si-Ali,
  • Raphaël Scharfmann,
  • Bertrand Cosson

DOI
https://doi.org/10.3389/fendo.2022.949097
Journal volume & issue
Vol. 13

Abstract

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Pancreatic beta cell response to glucose is critical for the maintenance of normoglycemia. A strong transcriptional response was classically described in rodent models but, interestingly, not in human cells. In this study, we exposed human pancreatic beta cells to an increased concentration of glucose and analysed at a global level the mRNAs steady state levels and their translationalability. Polysome profiling analysis showed an early acute increase in protein synthesis and a specific translation regulation of more than 400 mRNAs, independently of their transcriptional regulation. We clustered the co-regulated mRNAs according to their behaviour in translation in response to glucose and discovered common structural and sequence mRNA features. Among them mTOR- and eIF2-sensitive elements have a predominant role to increase mostly the translation of mRNAs encoding for proteins of the translational machinery. Furthermore, we show that mTOR and eIF2α pathways are independently regulated in response to glucose, participating to a translational reshaping to adapt beta cell metabolism. The early acute increase in the translation machinery components prepare the beta cell for further protein demand due to glucose-mediated metabolism changes.

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