IL-17 attenuates degradation of ARE-mRNAs by changing the cooperation between AU-binding proteins and microRNA16.
PLoS Genet
; 9(9): e1003747, 2013.
Article
em En
| MEDLINE
| ID: mdl-24086143
ABSTRACT
Interleukin 17A (IL-17), a mediator implicated in chronic and severe inflammatory diseases, enhances the production of pro-inflammatory mediators by attenuating decay of the encoding mRNAs. The decay of many of these mRNAs depends on proteins (AUBps) that target AU-rich elements in the 3'-untranslated region of mRNAs and facilitate either mRNA decay or stabilization. Here we show that AUBps and the target mRNA assemble in a novel ribonucleoprotein complex in the presence of microRNA16 (miR16), which leads to the degradation of the target mRNA. Notably, IL-17 attenuates miR16 expression and promotes the binding of stabilizing AUBps over that of destabilizing AUBps, reducing mRNA decay. These findings indicate that miR16 independently of a seed sequence, directs the competition between degrading and stabilizing AUBps for target mRNAs. Since AUBps affect expression of about 8% of the human transcriptome and miR16 is ubiquitously expressed, IL-17 may in addition to inflammation affect many other cellular processes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-17
/
MicroRNAs
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Elementos Ricos em Adenilato e Uridilato
/
Inflamação
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article