IL-17 Attenuates Degradation of ARE-mRNAs by Changing the Cooperation between AU-Binding Proteins and microRNA16

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. © 2013 chowdhury et al.