Key Laboratory of Chemical Biology and Molecular Engineering, Ministry of Education, China.
Biochem Biophys Res Commun. 2013 May 24;435(1):16-20. doi: 10.1016/j.bbrc.2013.03.129. Epub 2013 Apr 10.
Nonsense-mediated mRNA decay (NMD) is a cellular response mechanism that eliminates aberrant mRNA transcripts and thereby prevents the production of potentially deleterious C-terminally truncated proteins. The phosphatidylinositol 3-kinase-related protein kinase SMG1 is considered to be an essential factor in the NMD pathway. We demonstrate that the brain-enriched microRNA, miRNA-125 (miRNA-125a and miRNA-125b) is a bona fide negative regulator of SMG1 in humans. Down-regulation of SMG1 expression is mediated by miRNA-125 binding to a microRNA response element in the 3' untranslated region of SMG1 mRNA, which leads to degradation of the SMG1 mRNA. In human cells, overexpression of miR-125 represses the endogenous levels of SMG1 protein and suppresses the NMD pathway; however, knockdown of miR-125 up-regulates the NMD pathway. These results suggest the existence of an RNA circuit linking the microRNA and NMD pathways.
无意义介导的 mRNA 衰减（NMD）是一种细胞反应机制，可消除异常的 mRNA 转录本，从而防止产生潜在有害的 C 末端截断蛋白。磷酸肌醇 3-激酶相关蛋白激酶 SMG1 被认为是 NMD 途径中的必需因素。我们证明，富含大脑的 microRNA，miRNA-125（miRNA-125a 和 miRNA-125b）是人类中 SMG1 的真正负调控因子。SMG1 表达的下调是由 miRNA-125 与 SMG1 mRNA 3'非翻译区中的 microRNA 反应元件结合介导的，这导致 SMG1 mRNA 的降解。在人细胞中，miR-125 的过表达抑制内源性 SMG1 蛋白的水平并抑制 NMD 途径；然而，miR-125 的敲低上调 NMD 途径。这些结果表明存在一个 RNA 回路将 microRNA 和 NMD 途径联系起来。
