Elcheva Irina, Goswami Srikanta, Noubissi Felicite K, Spiegelman Vladimir S
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
Mol Cell. 2009 Jul 31;35(2):240-6. doi: 10.1016/j.molcel.2009.06.007.
miRNAs are largely known to base pair with the 3'UTR of target mRNAs, downregulating their stability and translation. mRNA of betaTrCP1 ubiquitin ligase is very unstable, but unlike the majority of mRNAs where 3'UTR determines the rate of mRNA turnover, betaTrCP1 mRNA contains cis-acting destabilizing elements within its coding region. Here we show that degradation of mRNA of betaTrCP1 is miRNA dependent and identify miR-183 as a microRNA that interacts with the coding region of betaTrCP1 mRNA. Argonaute2 interacts with the same region of betaTrCP1 mRNA in an miR-183-dependent manner. Inhibition of miR-183 function or disruption of the miR-183-binding site stabilizes betaTrCP1 mRNA and elevates betaTrCP1 levels, resulting in activation of the SCF(betaTrCP) E3 ubiquitin ligase. We previously showed that the RNA-binding protein CRD-BP binds to the coding region of betaTrCP1 mRNA and stabilizes it. Here we demonstrate that CRD-BP prevents degradation of betaTrCP1 mRNA by attenuating its miR-183-dependent interaction with Ago2.
众所周知，微小RNA（miRNA）主要与靶mRNA的3'非翻译区（3'UTR）碱基配对，从而下调其稳定性和翻译水平。β-转导素重复序列包含蛋白1（betaTrCP1）泛素连接酶的mRNA非常不稳定，但与大多数由3'UTR决定mRNA周转速度的mRNA不同，betaTrCP1 mRNA在其编码区域内含有顺式作用的不稳定元件。在此我们表明，betaTrCP1 mRNA的降解是miRNA依赖性的，并鉴定出miR-183是一种与betaTrCP1 mRNA编码区域相互作用的微小RNA。AGO2蛋白以miR-183依赖的方式与betaTrCP1 mRNA的相同区域相互作用。抑制miR-183功能或破坏miR-183结合位点可稳定betaTrCP1 mRNA并提高betaTrCP1水平，从而导致SCF（betaTrCP）E3泛素连接酶的激活。我们之前表明，RNA结合蛋白CRD-BP与betaTrCP1 mRNA的编码区域结合并使其稳定。在此我们证明，CRD-BP通过减弱其与AGO2的miR-183依赖性相互作用来防止betaTrCP1 mRNA的降解。
