美国哥伦比亚大学Liang Tong、北卡罗来纳大学教堂山分校Zbigniew Dominski和洛克菲勒大学Thomas Walz课题组合作，解析了活跃的人组蛋白前体信使RNA（pre-mRNA）3'末端加工机器的结构。相关论文2020年2月7日发表于国际学术期刊《科学》上。

他们利用13种重组蛋白和2种RNA重建了活跃的人组蛋白前pre-mRNA加工机器，并通过冷冻电镜确定了其结构。整体结构高度不对称，类似于带有一个长柄的双耳瓶。他们在核酸内切酶的活性位点捕获了pre-mRNA，准备进行裂解，该酶是裂解和聚腺苷酸化特异性因子的73-千道尔顿亚基。核酸内切酶和整个切割模块经历了广泛的重排激活，通过识别真正的pre-mRNA和U7小核RNA（snRNA）之间的双链体而触发。他们的研究对于理解经典和snRNA 3'-末端加工也具有显著意义。

据了解，后生复制依赖的组蛋白pre-mRNA的3'末端加工机器包含U7小核糖核蛋白，并与经典的裂解和聚腺苷酸化机制共享关键的裂解模块。

附：英文原文

Title: Structure of an active human histone pre-mRNA 3′-end processing machinery

Author: Yadong Sun, Yixiao Zhang, Wei Shen Aik, Xiao-Cui Yang, William F. Marzluff, Thomas Walz, Zbigniew Dominski, Liang Tong

Issue&Volume: 2020/02/07

Abstract: The 3′-end processing machinery for metazoan replication-dependent histone precursor messenger RNAs (pre-mRNAs) contains the U7 small nuclear ribonucleoprotein and shares the key cleavage module with the canonical cleavage and polyadenylation machinery. We reconstituted an active human histone pre-mRNA processing machinery using 13 recombinant proteins and two RNAs and determined its structure by cryo–electron microscopy. The overall structure is highly asymmetrical and resembles an amphora with one long handle. We captured the pre-mRNA in the active site of the endonuclease, the 73-kilodalton subunit of the cleavage and polyadenylation specificity factor, poised for cleavage. The endonuclease and the entire cleavage module undergo extensive rearrangements for activation, triggered through the recognition of the duplex between the authentic pre-mRNA and U7 small nuclear RNA (snRNA). Our study also has notable implications for understanding canonical and snRNA 3′-end processing.

DOI: 10.1126/science.aaz7758

Source: https://science.sciencemag.org/content/367/6478/700