MicroRNA 15a/16-1 As Post-transcriptional Regulators Of T Cell Activity And Proliferative Capacity
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2022
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University of Hawaii at Manoa
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Micro-RNA (miR) is a small RNA molecule whose origin comes from the genome. The miR serves as a post-transcriptional regulator of cellular processes. In this study, we investigated the miRs produced during T cell activation and the mRNAs they target. Following 18 hours of activation by T cell receptors, we measured 48 miRs decreased, and three miRs increased. The study focused on two of the decreased miRs (miR 15a/16-1) that play a role in B cell lymphomas, thus having the best potential to affect T cell proliferation and expansion. Using doxycycline-induced transgenes, we developed a mouse model to investigate the effects of exogenous miR 15a/16-1 on T cells using gain-of-function experiments. The model was also used to identify target mRNAs involved in the proliferation and expansion of T cells. We identified MEK1 as a significant miR-15a/16 target. As a result, MEK1 regulation by miR-15a/16-1, ERK1/2, and ELK1 protein phosphorylation levels were decreased 25 % and 50% respectively. In conclusion, these results suggest that T cell receptor (TCR) stimulation decreases miR-15a/16 levels early in T cell activation to facilitate increased MEK1, ERK1/2, and ELK1. This decrease in miR-15a/16-1 level promotes a robust proliferation capacity dependent on sustained activation of MEK1-ERK1/2-ELK1 signaling.
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MicroRNA, Mitogen-activated protein kinases, Cell interaction, T cells
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