Converging pathways involving microRNA-206 and the RNA-binding protein KSRP control post-transcriptionally utrophin A expression in skeletal muscle.
Converging pathways involving microRNA-206 and the RNA-binding protein KSRP control post-transcriptionally utrophin A expression in skeletal muscle.
复制标题
DOI：
10.1093/nar/gkt1350
复制
发表时间：
2014-04
影响因子：
14.9
通讯作者：
Jasmin BJ
中科院分区：
文献类型：
--
作者：
Amirouche A;Tadesse H;Miura P;Bélanger G;Lunde JA;Côté J;Jasmin BJ
先前有几篇报道强调了miR-206在培养细胞中utrophin A的转录后下调中的潜在作用。沿着这些路线，我们最近确定了K同源剪接调节蛋白（KSRP）作为一个重要的负调控在转录后控制的肌营养蛋白A在骨骼肌。我们试图确定这两种途径是否共同作用，下调肌营养蛋白A在骨骼肌中的表达。令人惊讶的是，我们发现miR-206在培养细胞和营养不良肌纤维中的过表达导致内源性utrophin A水平的上调。我们进一步表明，这种utrophin A的上调是由于miR-206与位于KSRP 3′-UTR（非翻译区）的保守位点结合，从而导致随后KSRP表达的抑制。这种miR-206介导的KSRP水平的降低反过来导致utrophin A表达的增加，这是由于这种不稳定的RNA结合蛋白的活性降低。我们的工作表明，miR-206可以在通过其3′-UTR直接抑制utrophin A表达和通过降低KSRP的可用性以及与位于utrophin A 3′-UTR内的富含AU的元件相互作用激活其表达之间振荡。因此，我们的研究表明，两个明显的负转录后途径可以作为分子开关，导致抑制或激活utrophin A的表达。
Several reports have previously highlighted the potential role of miR-206 in the post-transcriptional downregulation of utrophin A in cultured cells. Along those lines, we recently identified K-homology splicing regulator protein (KSRP) as an important negative regulator in the post-transcriptional control of utrophin A in skeletal muscle. We sought to determine whether these two pathways act together to downregulate utrophin A expression in skeletal muscle. Surprisingly, we discovered that miR-206 overexpression in cultured cells and dystrophic muscle fibers causes upregulation of endogenous utrophin A levels. We further show that this upregulation of utrophin A results from the binding of miR-206 to conserved sites located in the 3′-UTR (untranslated region) of KSRP, thus causing the subsequent inhibition of KSRP expression. This miR-206-mediated decrease in KSRP levels leads, in turn, to an increase in the expression of utrophin A due to a reduction in the activity of this destabilizing RNA-binding protein. Our work shows that miR-206 can oscillate between direct repression of utrophin A expression via its 3′-UTR and activation of its expression through decreased availability of KSRP and interactions with AU-rich elements located within the 3′-UTR of utrophin A. Our study thus reveals that two apparent negative post-transcriptional pathways can act distinctively as molecular switches causing repression or activation of utrophin A expression.
登录
查看更多内容
影响因子：
3.7
作者：
Basu U;Lozynska O;Moorwood C;Patel G;Wilton SD;Khurana TS
通讯作者：
Khurana TS
DOI：
10.1083/jcb.200603008
发表时间：
2006-08-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim HK;Lee YS;Sivaprasad U;Malhotra A;Dutta A
通讯作者：
Dutta A
影响因子：
4.8
作者：
Amirouche, Adel;Durieux, Anne-Cecile;Freyssenet, Damien
通讯作者：
Freyssenet, Damien
DOI：
10.1083/jcb.200911036
发表时间：
2010-09-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen JF;Tao Y;Li J;Deng Z;Yan Z;Xiao X;Wang DZ
通讯作者：
Wang DZ
影响因子：
3.5
作者：
Chakkalakal, JV;Michel, SA;Jasmin, BJ
通讯作者：
Jasmin, BJ