Regulation of miR-181a expression in T cell aging.
Nat Commun
; 9(1): 3060, 2018 08 03.
Article
em En
| MEDLINE
| ID: mdl-30076309
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
MicroRNAs
Limite:
Adult
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Aged
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Aged80
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article