当前位置: X-MOL 学术Science › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Structure of an active human histone pre-mRNA 3′-end processing machinery
Science ( IF 56.9 ) Pub Date : 2020-02-06 , DOI: 10.1126/science.aaz7758
Yadong Sun 1 , Yixiao Zhang 2 , Wei Shen Aik 1 , Xiao-Cui Yang 3 , William F Marzluff 3, 4 , Thomas Walz 2 , Zbigniew Dominski 3, 4 , Liang Tong 1
Affiliation  

Architecture of an mRNA processor The 3′-end processing of the three major classes of RNA polymerase II transcripts in metazoan cells—polyadenylated messenger RNAs (mRNAs), histone mRNAs, and small nuclear RNAs (snRNAs)—requires three distinct machineries that share common features. Sun et al. reconstituted the active human histone pre-mRNA 3′-end processing machinery and solved its structure at near-atomic resolution by cryo–electron microscopy. This structure provides a basis for understanding the mechanism of the shared catalytic reactions between histone pre-mRNA and canonical pre-mRNA and snRNA 3′-end processing machineries. Science, this issue p. 700 An active human histone pre-mRNA 3′-end processing machinery was reconstituted and its structure solved at near-atomic resolution. 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.

中文翻译:

活性人组蛋白前体 mRNA 3'-末端加工机制的结构

mRNA 处理器的架构 后生动物细胞中三大类 RNA 聚合酶 II 转录物——多腺苷酸化信使 RNA (mRNA)、组蛋白 mRNA 和小核 RNA (snRNA)——的 3' 端加工需要三种不同的机器,它们具有共同的特点。特征。孙等人。重建了活跃的人类组蛋白前体 mRNA 3'-末端加工机制,并通过冷冻电子显微镜以近原子分辨率解​​析了其结构。这种结构为理解组蛋白前体 mRNA 与经典前体 mRNA 和 snRNA 3'-末端加工机制之间共享催化反应的机制提供了基础。科学,这个问题 p。700 一个活跃的人类组蛋白前体 mRNA 3'-末端加工机制被重建,其结构以近原子分辨率解​​析。后生动物复制依赖性组蛋白前体信使 RNA(pre-mRNA)的 3' 端加工机制包含 U7 小核核糖核蛋白,并与经典切割和聚腺苷酸化机制共享关键的切割模块。我们使用 13 种重组蛋白和两种 RNA 重建了一个活跃的人类组蛋白前 mRNA 加工机制,并通过冷冻电子显微镜确定了其结构。整体结构高度不对称,类似于一个长柄的双耳瓶。我们在核酸内切酶的活性位点捕获了前体 mRNA,即切割和聚腺苷酸化特异性因子的 73 千道尔顿亚基,准备切割。核酸内切酶和整个切割模块经历了广泛的重排以激活,通过识别真实的前 mRNA 和 U7 小核 RNA (snRNA) 之间的双链体触发。我们的研究对于理解规范和 snRNA 3'-末端加工也具有显着意义。
更新日期:2020-02-06
down
wechat
bug