Regulation of miR-181a expression in T cell aging

Nat Commun. 2018 Aug 3;9(1):3060. doi: 10.1038/s41467-018-05552-3.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Differentiation / genetics
  • Cellular Senescence / genetics
  • Chromosomes, Human, Pair 1
  • HEK293 Cells
  • Humans
  • Lymphocyte Activation
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Signal Transduction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism
  • Up-Regulation
  • YY1 Transcription Factor / metabolism
  • Young Adult

Substances

  • MIrn181 microRNA, human
  • MicroRNAs
  • YY1 Transcription Factor
  • YY1 protein, human