To initiate co-transcriptional splicing, RNA polymerase II (Pol II) recruits U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent pre-mRNA. Here we report the cryo-EM 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 5' splice site in pre-mRNA near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5' splice site, leading to formation of an intron loop. Loop formation may facilitate scanning of the nascent pre-mRNA for the 3' splice site and enable prespliceosome assembly and functional pairing of distant intron ends. Our results provide a starting point for a mechanistic analysis of co-transcriptional splicing and the biogenesis of mRNA isoforms during alternative splicing.

中文翻译：

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转录RNA聚合酶II-U1 snRNP复合物的结构

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）募集到新生的pre-mRNA。在这里，我们报告哺乳动物转录Pol II-U1 snRNP复合体的低温EM结构。该结构表明Pol II和U1 snRNP直接相互作用。这种相互作用将前mRNA中的5'剪接位点置于Pol II的RNA出口位点附近。前mRNA的延伸保留了5'剪接位点，导致内含子环的形成。环形成可以促进新生的pre-mRNA的3'剪接位点的扫描，并使剪接体组装和远距离内含子末端的功能配对成为可能。我们的结果为共转录剪接和替代剪接过程中mRNA亚型的生物发生机制分析提供了一个起点。