TNF-alpha stimulation inhibits siRNA-mediated RNA interference through a mechanism involving poly-(A) tail stabilization
van den Berg, A
- 生命科学－已发表论文 
The control of mRNA stability is a complex biological process that involves numerous factors, including rnicroRNA (miRNA) and short interfering RNA (siRNA). Here, we show that short interfering RNA (siRNA) and rnicroRNA share some similarities in their response to cellular stress. rniR16 expedites the degradation of mRNAs containing AU-rich elements (ARE) in their 31 untranslated region (UTR). si20 is an siRNA designed to target a non-ARE sequence in the TNF 3'UTR. We found that both si20 and miR16/ARE-mediated degradation of mRNAs can be inhibited by stimulating cells with different stresses. By analyzing TNF-alpha stimulation-mediated stabilization of si20- and miR16-targeted mRNA, we show that this stabilization is not caused by modifying si20 and miR16 loading into Ago2 complexes, or mRNA targeting to Ago2, but by inhibiting mRNA deadenylation. This is the first report showing that a specific siRNA-mediated mRNA degradation can be regulated by inflammatory stimuli, and that deadenylation is involved in this siRNA-mediated mRNA decay. (C) 2008 Elsevier B.V. All rights reserved.