Differential Regulation of Two Arms of mTORC1 Pathway Fine-Tunes Global Protein Synthesis in Resting B Lymphocytes

Gagan Dev, Amanpreet Singh Chawla, Suman Gupta, Vineeta Bal, Anna George, Satyajit Rath, G Aneeshkumar Arimbasseri (Lead / Corresponding author)

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Abstract

Protein synthesis is tightly regulated by both gene-specific and global mechanisms to match the metabolic and proliferative demands of the cell. While the regulation of global protein synthesis in response to mitogen or stress signals is relatively well understood in multiple experimental systems, how different cell types fine-tune their basal protein synthesis rate is not known. In a previous study, we showed that resting B and T lymphocytes exhibit dramatic differences in their metabolic profile, with implications for their post-activation function. Here, we show that resting B cells, despite being quiescent, exhibit increased protein synthesis in vivo as well as ex vivo. The increased protein synthesis in B cells is driven by mTORC1, which exhibits an intermediate level of activation in these cells when compared with resting T cells and activated B cells. A comparative analysis of the transcriptome and translatome of these cells indicates that the genes encoding the MHC Class II molecules and their chaperone CD74 are highly translated in B cells. These data suggest that the translatome of B cells shows enrichment for genes associated with antigen processing and presentation. Even though the B cells exhibit higher mTORC1 levels, they prevent the translational activation of TOP mRNAs, which are mostly constituted by ribosomal proteins and other translation factors, by upregulating 4EBP1 levels. This mechanism may keep the protein synthesis machinery under check while enabling higher levels of translation in B cells.

Original languageEnglish
Article number16017
Number of pages13
JournalInternational Journal of Molecular Sciences
Volume23
Issue number24
DOIs
Publication statusPublished - 16 Dec 2022

Keywords

  • Mechanistic Target of Rapamycin Complex 1/metabolism
  • Ribosomal Proteins/metabolism
  • Protein Biosynthesis
  • T-Lymphocytes
  • B-Lymphocytes

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