德国马克斯普朗克研究所Patrick Cramer团队解析出RNA聚合酶II–U1 snRNP复合物的结构。该项研究成果发表在2021年1月15日出版的《科学》杂志上。

研究人员表示，为了启动共转录剪接，RNA聚合酶II（Pol II）将U1小核糖核蛋白颗粒（U1 snRNP）招募到新生的前体信使RNA（pre-mRNA）中。

研究人员报道了哺乳动物转录Pol II–U1 snRNP复合体的冷冻电镜结构。该结构表明Pol II和U1 snRNP直接发生相互作用。该相互作用将前mRNA 5'剪接位点置于Pol II的RNA出口位点附近。pre-mRNA的延伸保留了5'剪接位点，导致“内含子环”的形成。环形成可促进新生mRNA的3'剪接位点扫描、内含子远末端的功能配对和剪接体组装。

这些结果为共转录剪接体组装以及mRNA亚型的生物发生机制（通过选择性剪接介导）提供了一个研究起点。

附：英文原文

Title: Structure of a transcribing RNA polymerase II–U1 snRNP complex

Author: Suyang Zhang, Shintaro Aibara, Seychelle M. Vos, Dmitry E. Agafonov, Reinhard Lührmann, Patrick Cramer

Issue&Volume: 2021/01/15

Abstract: To initiate cotranscriptional splicing, RNA polymerase II (Pol II) recruits the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent precursor messenger RNA (pre-mRNA). Here, we report the cryo–electron microscopy structure of a mammalian transcribing Pol II–U1 snRNP complex. The structure reveals that Pol II and U1 snRNP interact directly. This interaction positions the pre-mRNA 5′ splice site near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5′ splice site, leading to the formation of a “growing intron loop.” Loop formation may facilitate scanning of nascent pre-mRNA for the 3′ splice site, functional pairing of distant intron ends, and prespliceosome assembly. Our results provide a starting point for a mechanistic analysis of cotranscriptional spliceosome assembly and the biogenesis of mRNA isoforms by alternative splicing.

DOI: 10.1126/science.abf1870

Source: https://science.sciencemag.org/content/371/6526/305