Allain F H, Gubser C C, Howe P W, Nagai K, Neuhaus D, Varani G
MRC Laboratory of Molecular Biology, Cambridge, UK.
Nature. 1996 Apr 18;380(6575):646-50. doi: 10.1038/380646a0.
Many proteins involved in pre-mRNA processing contain one or more copies of a 70-90-amino-acid alphabeta module called the ribonucleoprotein domain. RNA maturation depends on the specific recognition by ribonucleoproteins of RNA elements within pre-mRNAs and small nuclear RNAs. The human U1A protein binds an RNA hairpin during splicing, and regulates its own expression by binding an internal loop in the 3'-untranslated region of its pre-mRNA, preventing polyadenylation. Here we report the nuclear magnetic resonance structure of the complex between the regulatory element of the U1A 3'-untranslated region (UTR) and the U1A protein RNA-binding domain. Specific intermolecular recognition requires the interaction of the variable loops of the ribonucleoprotein domain with the well-structured helical regions of the RNA. Formation of the complex then orders the flexible RNA single-stranded loop against the protein beta-sheet surface, and reorganizes the carboxy-terminal region of the protein to maximize surface complementarity and functional group recognition.
许多参与前体mRNA加工的蛋白质含有一个或多个被称为核糖核蛋白结构域的70-90个氨基酸的αβ模块拷贝。RNA成熟依赖于核糖核蛋白对前体mRNA和小核RNA内RNA元件的特异性识别。人类U1A蛋白在剪接过程中结合一个RNA发夹，并通过结合其前体mRNA 3'-非翻译区的一个内环来调节自身表达，从而阻止多聚腺苷酸化。在此，我们报道了U1A 3'-非翻译区（UTR）调控元件与U1A蛋白RNA结合结构域之间复合物的核磁共振结构。特异性分子间识别需要核糖核蛋白结构域的可变环与RNA结构良好的螺旋区域相互作用。复合物的形成随后使柔性RNA单链环相对于蛋白质β-折叠表面有序排列，并重新组织蛋白质的羧基末端区域，以最大化表面互补性和官能团识别。
