Grosset C, Chen C Y, Xu N, Sonenberg N, Jacquemin-Sablon H, Shyu A B
Department of Biochemistry and Molecular Biology, The University of Texas Houston Medical School 77030, USA.
Cell. 2000 Sep 29;103(1):29-40. doi: 10.1016/s0092-8674(00)00102-1.
mRNA turnover mediated by the major protein-coding-region determinant of instability (mCRD) of the c-fos proto-oncogene transcript illustrates a functional interplay between mRNA turnover and translation. We show that the function of mCRD depends on its distance from the poly(A) tail. Five mCRD-associated proteins were identified: Unr, a purine-rich RNA binding protein; PABP, a poly(A) binding protein; PAIP-1, a poly(A) binding protein interacting protein; hnRNP D, an AU-rich element binding protein; and NSAP1, an hnRNP R-like protein. These proteins form a multiprotein complex. Overexpression of these proteins stabilized mCRD-containing mRNA by impeding deadenylation. We propose that a bridging complex forms between the poly(A) tail and the mCRD and ribosome transit disrupts or reorganizes the complex, leading to rapid RNA deadenylation and decay.
由原癌基因c-fos转录本的主要蛋白质编码区不稳定决定因素（mCRD）介导的mRNA周转说明了mRNA周转与翻译之间的功能相互作用。我们发现mCRD的功能取决于其与多聚腺苷酸（poly(A)）尾的距离。鉴定出了5种与mCRD相关的蛋白质：富含嘌呤的RNA结合蛋白Unr；多聚腺苷酸结合蛋白PABP；多聚腺苷酸结合蛋白相互作用蛋白PAIP-1；富含AU元件结合蛋白hnRNP D；以及hnRNP R样蛋白NSAP1。这些蛋白质形成了一个多蛋白复合物。这些蛋白质的过表达通过阻碍去腺苷酸化使含有mCRD的mRNA稳定。我们提出，在多聚腺苷酸尾和mCRD之间形成了一个桥接复合物，核糖体的通过会破坏或重组该复合物，导致RNA快速去腺苷酸化和降解。
