TNF-alpha stimulation inhibits siRNA-mediated RNA interference through a mechanism involving poly-(A) tail stabilization.

@article{citeulike:2729327, abstract = {The control of mRNA stability is a complex biological process that involves numerous factors, including microRNA (miRNA) and short interfering RNA (siRNA). Here, we show that short interfering RNA (siRNA) and microRNA share some similarities in their response to cellular stress. miR16 expedites the degradation of mRNAs containing AU-rich elements (ARE) in their 3' unltranslated 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.}, address = {Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, CA, USA; Viral Development Unit, R\&D Department, GlaxoSmithKline Biologicals, 15, rue de l'institut, B-1340 Rixensart, Belgium.}, author = {Mols, Johann and Berg, Arjen van den V. and Otsuka, Motoyuki and Zheng, Min and Chen, Jianming and Han, Jiahuai }, citeulike-article-id = {2729327}, doi = {10.1016/j.bbagrm.2008.03.007}, issn = {0006-3002}, journal = {Biochimica et biophysica acta}, keywords = {polya, rnai, tnf-alpha}, month = {April}, posted-at = {2008-04-28 10:13:30}, priority = {2}, title = {TNF-alpha stimulation inhibits siRNA-mediated RNA interference through a mechanism involving poly-(A) tail stabilization.}, url = {http://dx.doi.org/10.1016/j.bbagrm.2008.03.007}, year = {2008} }

TY - JOUR ID - citeulike:2729327 L3 - citeulike-article-id:2729327 TI - TNF-alpha stimulation inhibits siRNA-mediated RNA interference through a mechanism involving poly-(A) tail stabilization. JF - Biochimica et biophysica acta AD - Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, CA, USA; Viral Development Unit, R&D Department, GlaxoSmithKline Biologicals, 15, rue de l'institut, B-1340 Rixensart, Belgium. SN - 0006-3002 N2 - The control of mRNA stability is a complex biological process that involves numerous factors, including microRNA (miRNA) and short interfering RNA (siRNA). Here, we show that short interfering RNA (siRNA) and microRNA share some similarities in their response to cellular stress. miR16 expedites the degradation of mRNAs containing AU-rich elements (ARE) in their 3' unltranslated 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. KW - polya KW - rnai KW - tnf-alpha AU - Mols, Johann AU - Berg, Arjen van den AU - Otsuka, Motoyuki AU - Zheng, Min AU - Chen, Jianming AU - Han, Jiahuai PY - 2008/04/01/ UR - http://dx.doi.org/10.1016/j.bbagrm.2008.03.007 ER -