Pérez-Cañadillas José Manuel
Laboratory of Molecular Biology, Medical Research Council, Cambridge, UK.
EMBO J. 2006 Jul 12;25(13):3167-78. doi: 10.1038/sj.emboj.7601190. Epub 2006 Jun 22.
The recognition of specific signals encoded within the 3'-untranslated region of the newly transcribed mRNA triggers the assembly of a multiprotein machine that modifies its 3'-end. Hrp1 recognises one of such signals, the so-called polyadenylation enhancement element (PEE), promoting the recruitment of other polyadenylation factors in yeast. The molecular bases of this interaction are revealed here by the solution structure of a complex between Hrp1 and an oligonucleotide mimicking the PEE. Six consecutive bases (AUAUAU) are specifically recognised by two RNA-binding domains arranged in tandem. Both protein and RNA undergo significant conformational changes upon complex formation with a concomitant large surface burial of RNA bases. Key aspects of RNA specificity can be explained by the presence of intermolecular aromatic-aromatic contacts and hydrogen bonds. Altogether, the Hrp1-PEE structure represents one of the first steps towards understanding of the assembly of the cleavage and polyadenylation machinery at the atomic level.
对新转录的mRNA 3'-非翻译区编码的特定信号的识别触发了一个多蛋白机器的组装,该机器会修饰其3'-末端。Hrp1识别其中一种这样的信号,即所谓的聚腺苷酸化增强元件(PEE),促进酵母中其他聚腺苷酸化因子的募集。Hrp1与模拟PEE的寡核苷酸之间复合物的溶液结构揭示了这种相互作用的分子基础。六个连续的碱基(AUAUAU)被两个串联排列的RNA结合结构域特异性识别。蛋白质和RNA在形成复合物时都会发生显著的构象变化,同时RNA碱基会大量埋藏在表面。RNA特异性的关键方面可以通过分子间芳香-芳香接触和氢键的存在来解释。总之,Hrp1-PEE结构代表了在原子水平上理解切割和聚腺苷酸化机器组装的第一步。