[HTML][HTML] Regulation of miR-181a expression in T cell aging

Z Ye, G Li, C Kim, B Hu, RR Jadhav… - Nature …, 2018 - nature.com
Z Ye, G Li, C Kim, B Hu, RR Jadhav, CM Weyand, JJ Goronzy
Nature communications, 2018nature.com
MicroRNAs have emerged as key regulators in T cell development, activation, and
differentiation, with miR-181a having a prominent function. By targeting several signaling
pathways, miR-181a is an important rheostat controlling T cell receptor (TCR) activation
thresholds in thymic selection as well as peripheral T cell responses. A decline in miR-181a
expression, due to reduced transcription of pri-miR-181a, accounts for T cell activation
defects that occur with older age. Here we examine the transcriptional regulation of miR …
Abstract
MicroRNAs have emerged as key regulators in T cell development, activation, and differentiation, with miR-181a having a prominent function. By targeting several signaling pathways, miR-181a is an important rheostat controlling T cell receptor (TCR) activation thresholds in thymic selection as well as peripheral T cell responses. A decline in miR-181a expression, due to reduced transcription of pri-miR-181a, accounts for T cell activation defects that occur with older age. Here we examine the transcriptional regulation of miR-181a expression and find a putative pri-miR-181a enhancer around position 198,904,300 on chromosome 1, which is regulated by a transcription factor complex including YY1. The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Partial silencing of YY1 in T cells from young individuals reproduces the signaling defects seen in older T cells. In conclusion, YY1 controls TCR signaling by upregulating miR-181a and dampening negative feedback loops mediated by miR-181a targets.
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