Kubota Satoshi, Mukudai Yoshiki, Moritani Norifumi H, Nakao Kyouji, Kawata Kazumi, Takigawa Masaharu
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine and Dentistry, Japan.
FEBS Lett. 2005 Jul 4;579(17):3751-8. doi: 10.1016/j.febslet.2005.05.068.
The cis-acting element of structure-anchored repression (CAESAR) is a post-transcriptional regulatory element of gene expression, which is located in the 3'-untranslated region (UTR) of the human ccn2 gene (ctgf/ccn2). In this report, the repression mechanism of CAESAR, as well as the structural requirement, was investigated. Removal of minor stem-loops from CAESAR resulted in proportional attenuation of the repressive function, whereas removal of the single bulge or modification of primary nucleotide sequence did not affect its functionality. In light of functional mechanism, CAESAR exerted no significant effects on stability or nuclear export of the cis-linked mRNA. However, this element significantly interfered with the association of such mRNA on ribosome and slowed down the translation process thereafter in vitro. A translation repression mechanism by RNA secondary structure to determine the basal ctgf/ccn2 expression level was uncovered herein.
结构锚定抑制顺式作用元件(CAESAR)是基因表达的一种转录后调控元件,位于人类ccn2基因(ctgf/ccn2)的3'非翻译区(UTR)。在本报告中,对CAESAR的抑制机制及其结构要求进行了研究。从CAESAR中去除小的茎环会导致抑制功能成比例减弱,而去除单个凸起或改变初级核苷酸序列并不影响其功能。根据功能机制,CAESAR对顺式连接的mRNA的稳定性或核输出没有显著影响。然而,该元件在体外显著干扰了此类mRNA与核糖体的结合,并随后减缓了翻译过程。本文揭示了一种由RNA二级结构决定基础ctgf/ccn2表达水平的翻译抑制机制。